SUBSTITUTED 2(5H)FURANONE, 2(5H)THIOPHENONE AND 2(5H)PYRROLONE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS ENDOTHELIN ANTAGONISTS

Abstract: Compounds of formula (I), or a tautomeric open chain keto-acid form thereof or a pharmaceutically acceptable salt thereof wherein: R1 is alkyl substituted or unsubstituted, straight, or branched, of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, phenyl substituted with from 1 to 5 substituents, naphthyl unsubstituted or substituted with from 1 to 5 substituents, or heteroaryl unsubstituted or substituted with from 1 to 5 substituents; R2 is alkyl substituted or unsubstituted, straight, or branched of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, aryl which is unsubstituted or substituted with from 1 to 5 substituents, heteroaryl wich is unsubstituted or substituted with from 1 to 3 substituents; R3 is alkyl substituted or unsubstituted, straight, or branched, of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, aryl which is unsubstituted or substituted with from 1 to 5 substituents, heteroaryl which is unsubstituted or substituted with from 1 to 3 substituents; R4 is hydrogen, hydroxy, halogen, SR5, OR5 wherein R5 is alkyl or substituted alkyl of from 1 to 7 carbon atoms, NR6R7 wherein R6 and R7 are each independently hydrogen, alkyl, substituted alkyl, substituted or unsubstituted phenyl, and (CH2)nOR5 wherein n is an integer of from 1 to 3; X is oxygen, S or NR8 wherein R8 is hydrogen, alkyl or substituted alkyl with the proviso that when R1 is monosubstituted phenyl and the substituent is p-methoxy, R3 is not unsubstituted phenyl, monosubstituted phenyl, or mesityl and with the further proviso when R2 is alkyl substituted, the substituent is not oxygen at the alpha -position to the furanone ring and with the further proviso that R1 and R3 are not both alkyl or alkyl substituted in the same molecule, their use as nonpeptide antagonists of endothelin I, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, myocardial ischemia, cerebral vasospasm, cerebral ischemia, cerebral infarction, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, stroke, and diabetes.

Description: SUBSTITUTED 2(5H)FURANONE, 2(5H)THI0PHEN0NE AND 2(5H)PYRR0L0NE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS ENDOTHELIN ANTAGONISTS CROSS-REFERENCE TO RELATED APPLICATIONS This is a continuation-in-part of United States Serial Number 08/217,578 filed March 24, 1994, which is a continuation-in-part of United States Serial Number 08/109,751 filed August 19, 1993, now abandoned. BACKGROUND OF THE INVENTION The present invention relates to novel antagonists of endothelin useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceu¬ tical methods of treatment. More particularly, the compounds of the present invention are antagonists of endothelin useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction and myocardial ischemia, cerebral vasospasm, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, and diabetes. Also, the compounds will be useful in cerebral ischemia or cerebral infarction resulting from a range of conditions such as thromboembolic or hemorrhagic stroke, cerebral vasospasm, head injury, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery, and cerebral trauma. Several studies have been reported with both peptide and non-peptide ET antagonists showing efficacy in various models of subarachnoid hemorrhage (SAH) . For example, BQ-123-prevents early cerebral vasospasm following SAH in various rat (Clozel M. , et al., Life Sci. 1993;52:825) and rabbit (Lee K.S., et al., Cerebral Vasospasm 1993:217; and Neurosurαery 1994; 34:108) models. FR 139317 significantly inhibited the vascoconstriction of the basilar artery after 7 days in a canine two-hemorrhage model of SAH (Nirei H. , et al., Life Sci. 1993;52:1869) . BQ-485 also significantly inhibited the vascoconstriction of the basilar artery after 7 days in a canine two-hemorrhage model of SAH (Yano, et al., Biochem Biophys. Res Commun. 1993; 195:969). Ro 46-2005 (Clozel M. , et al., Nature 1993;365:759) has been shown to prevent early cerebral vasospasm following SAH in the rat with no significant effect on systemic arterial blood pressure. Treatment with Ro 47-0203=Bosentan (Clozel et al., Circulation 1993;88(4) part 2:0907) to rabbits with SAH had a 36 ± 7% reduction of basilar artery cross-sectional area compared to sham rabbits. All of these studies show in vivo efficacy of endothelin antagonists in cerebral vasospasm resulting from SAH. Endothelin-1 (ET-1) , a potent vasoconstrictor, is a 21 amino acid bicyclic peptide that was first isolated from cultured porcine aortic endothelial cells. Endothelin-1, is one of a family of structurally similar bicyclic peptides which include; ET-2, ET-3, vasoactive intestinal contractor (VIC), and the sarafotoxins (SRTXs) . Endothelin is involved in many human disease states. Several in vivo studies with ET antibodies have been reported in disease models. Left coronary artery ligation and reperfusion to induce myocardial infarction in the rat heart, caused a 4- to 7-fold increase in endogenous endothelin levels. Administra- tion of ET antibody was reported to reduce the size of the infarction in a dose-dependent manner ( atanabe T., et al., "Endothelin in Myocardial Infarction," Nature (Lond.) 1990;344:114) . Thus, ET may be involved in the pathogenesis of congestive heart failure and myocardial ischemia (Margulies K.B., et al., "Increased Endothelin in Experimental Heart Failure, " Circulation 1990;82:2226) . Studies by Kon and colleagues using anti-ET antibodies in an ischemic kidney model, to deactivate endogenous ET, indicated the peptide's involvement in acute renal ischemic injury (Kon v., et al., "Glomerular Actions of Endothelin In Vivo," J. Clin. Invest. 1989;83:1762) . In isolated kidneys, preexposed to specific antiendothelin antibody and then challenged with cyclosporine, the renal perfusate flow and glomerular filtration rate increased, while renal resistance decreased as compared with isolated kidneys preexposed to a nonimmunized rabbit serum. The effec¬ tiveness and specificity of the anti-ET antibody were confirmed by its capacity to prevent renal deteriora- tion caused by a single bolus dose (150 pmol) of synthetic ET, but not by infusion of angiotensin II, norepinephrine, or the thromboxane A 2 mimetic U-46619 in isolated kidneys (Perico N. , et al., "Endothelin Mediates the Renal Vasoconstriction Induced by Cyclosporine in the Rat," J. Am. Soc. Nephrol. 1990;1:76) . Others have reported inhibition of ET-1 or ET-2-induced vasoconstriction in rat isolated thoracic aorta using a monoclonal antibody to ET-1 (Koshi T. , et al., "Inhibition of Endothelin (ET)-l and ET-2- Induced Vasoconstriction by Anti-ET-1 Monoclonal Antibody," Chem. Pharm. Bull. 1991;39:1295) . Combined administration of ET-1 and ET-1 antibody to rabbits showed significant inhibition of the blood pressure (BP) and renal blood flow responses (Miyamori I. , et al. , Systemic and Regional Effects of Endothelin in Rabbits: Effects of Endothelin Antibody," Clin. Exp. Pharmacol. Physiol. 1990;17:691) . Other investigators have reported that infusion of ET-specific antibodies into spontaneously hypertensive rats (SHR) decreased mean arterial pressure (MAP) , and increased glomerular filtration rate and renal blood flow. In the control study with normotensive Wistar-Kyoto rats (WKY) there were no significant changes in these parameters (Ohno A. Effects of Endothelin-Specific Antibodies and Endothelin in Spontaneously Hypertensive Rats," J. Tokyo Women's Med. Coll. 1991;61:951) . In addition, elevated levels of endothelin have been reported in several disease states (see Table I below) . Burnett and co-workers recently demonstrated that exogenous infusion of ET (2.5 ng/kg/mL) to anesthetized dogs, producing a doubling of the circulating concen¬ tration, did have biological actions (Lerman A. , et al., "Endothelin has Biological Actions at Patho- physiological Concentrations," Circulation 1991; 83:1808). Thus heart rate and cardiac output decreased in association with increased renal and systemic vascular resistances and antinatriuresis. These studies support a role for endothelin in the regulation of cardiovascular, renal, and endocrine function. In congestive heart failure in dogs and humans, a significant 2- to 3-fold elevation of circulating ET levels has been reported (Rodeheffer R.J. , et al., "Circulating Plasma Endothelin Correlates With the Severity of Congestive Heart Failure in Humans, " Am. J. Hypertension 1991;4:9A). The distribution of the two cloned receptor subtypes, termed ET A and ET B , have been studied extensively (Arai H., et al., Nature 1990;348:730, Sakurai T. , et al., Nature 1990;348:732) . The ET A , or vascular smooth muscle receptor, is widely distributed in cardiovascular tissues and in certain regions of the brain (Lin H.Y., et al., Proc. Natl. Acad. Sci. 1991;88:3185) . The ET B receptor, originally cloned from rat lung, has been found in rat cerebellum and in endothelial cells, although it is not known if the ET B receptors are the same from these sources. The human ET receptor subtypes have been cloned and expressed (Sakamoto A., et al., Biochem. Biophys. Res. Chem. 1991;178:656, Hosoda K. , et al., FEBS Lett. 1991;287:23) . The ET A receptor clearly mediates vasoconstriction and there have been a few reports implicating the ET B receptor in the initial vasodilatory response to ET (Takayanagi R. , et al., FEBS Lett. 1991;282:103) . However, recent data has shown that the ET B receptor can also mediate vasocon¬ striction in some tissue beds (Panek R.L., et al., Biochem. Biophys. Res. Commun. 1992;183 (2) :566) . A recent study showed that selective ET B agonists caused only vasodilation in the rat aortic ring, possibly through the release of EDRF from the endothelium (ibid) . Thus, reported selective ET B agonists, for example, the linear analog ET[1,3,11,15-Ala] and truncated analogs ET[6-21, 1,3,11,15-Ala] , ET[8-21,11,15-Ala] , and N-Acetyl- ET[10-21,11,15-Ala] caused vasorelaxation in isolated, endothelium-intact porcine pulmonary arteries (Saeki T., et al., Biochem. Biophys. Res. Commun. 1991;179:286) . However, some ET analogs are potent vasoconstrictors in the rabbit pulmonary artery, a tissue that appears to possess an ET B , nonselective type of receptor (ibid) . Plasma endothelin-1 levels were dramatically increased in a patient with malignant hemangioendo- thelioma (Nakagawa K. et al., Nippon Hifuka Gakkai Zasshi 1990;100:1453-1456). The ET receptor antagonist BQ-123 has been shown to block ET-1 induced bronchoconstriction and tracheal smooth muscle contraction in allergic sheep providing evidence for expected efficacy in bronchopulmonary diseases such as asthma (Noguchi, et al., Am. Rev. ResDir. Pis. 1992;145(4 Part 2) :A858) . Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations indicate a role for ET in renal constriction in preeclampsia (Clark B.A., et al., Am. J. Obstet. Gynecol. 1992;166:962-968). Plasma immunoreactive endothelin-1 concentrations are elevated in patients with sepsis and correlate with the degree of illness and depression of cardiac output (Pittett J., et al., Ann Surσ. 1991;213 (3) :262) . In addition the ET-1 antagonist BQ-123 has been evaluated in a mouse model of endotoxic shock. This ET A antagonist significantly increased the survival rate in this model (Toshiaki M. , et al., 20.12.90. EP 0 436 189 Al) . Endothelin is a potent agonist in the liver eliciting both sustained vasoconstriction of the hepatic vasculature and a significant increase in hepatic glucose output (Gandhi C.B., et al., Journal of Biological Chemistry 1990;265(29) :17432) . In addition increased levels of plasma ET-1 have been observed in microalbuminuric insulin-dependent diabetes mellitus patients indicating a role for ET in endocrine disorders such as diabetes (Collier A., et al., Diabetes Care 1992;15(8) :1038) . ET A antagonist receptor blockade has been found to produce an antihypertensive effect in normal to low renin models of hypertension with a time course similar to the inhibition of ET-1 pressor responses (Basil M.K., et al., J. Hypertension 1992; 10(Suppl 4): S49) . The endothelins have been shown to be arrhythmo- genic, and to have positive chronotropic and inotropic effects, thus ET receptor blockade would be expected to be useful in arrhythmia and other cardiovascular disorders (Han S.-P., et al., Life Sci. 1990;46:767) . The widespread localization of the endothelins and their receptors in the central nervous system and cere- brovascular circulation has been described (Nikolpv R.K., et al., Drucrs of Today 1992;28 (5) :303-310) . Intracerebroventricular administration of ET-1 in rats has been shown to evoke several behavioral effects. These factors strongly suggest a role for the ETs in neurological disorders. The potent vasoconstrictor action of ETs on isolated cerebral arterioles suggests the importance of these peptides in the regulation of cerebrovascular tone. Increased ET levels have been reported in some CNS disorders, i.e., in the CSF of patients with subarachnoid hemorrhage and in the plasma of women with preeclampsia. Stimulation with ET-3 under conditions of hypoglycemia have been shown to accelerate the development of striatal damage as a result of an influx of extracellular calcium. Circulating or locally produced ET has been suggested to contribute to regulation of brain fluid balance through effects on the choroid plexus and CSF produc¬ tion. ET-1 induced lesion development in a new model of local ischemia in the brain has been described. Circulating and tissue endothelin immunoreactivity is increased more than twofold in patients with advanced atherosclerosis (Lerman A., et al., New England J. Med. 1991;325:997-1001) . Increased endothelin immunoreactivity has also been associated with Buerger's disease (Kanno K. , et al., J. Amer. Med. Assoc. 1990;264:2868) and Raynaud's phenomenon (Zamora M.R., et al., Lancet 1990;336:1144-1147). An increase of circulating endothelin levels was observed in patients that underwent percutaneous transluminal coronary angioplasty (PTCA) (Tahara A. , et al., Metab. Clin. Exp. 1991;40:1235-1237. Increased plasma levels of endothelin have been measured in rats and humans (Stewart D.J., et al., Ann. Internal Medicine 1991;114:464-469) with pulmonary hypertension. Elevated levels of endothelin have also been measured in patients suffering from ischemic heart disease (Yasuda M. , et al., Amer. Heart J. 1990;119:801-806) and either stable or unstable angina (Stewart J.T. , et al., Br. Heart J. 1991;66:7-9). Infusion of an endothelin antibody 1 hour prior to and 1 hour after a 60 minute period of renal ischaemia resulted in changes in renal function versus control. In addition, an increase in glomerular platelet- activating factor was attributed to endothelin (Lopez- Farre A., et al., J. Physiology 1991;444:513-522). In patients with chronic renal failure as well as in patients on regular hemodialysis treatment mean plasma endothelin levels were significantly increased (Stockenhuber F., et al., Clin. Sci. (Lond.) 1992;82:255-258) . Local intra-arterial administration of endothelin has been shown to induce small intestinal mucosal damage in rats in a dose-dependent manner (Mirua S., et al., Digestion 1991;48:163-172). Furthermore, it has been shown that an anti-ET-1 antibody reduced ethanol-induced vasoconstriction in a concentration- dependent manner (Masuda E. , et al. , Am. J. Physiol. 1992;262:G785-G790) . Elevated endothelin levels have been observed in patients suffering from Crohn's disease and ulcerative colitis (Murch S.H., et al., Lancet 1992:339:381-384). Recently at the 3rd International Conference on Endothelin, Houston, Texas, February 1993, the nonpeptide endothelin antagonist RO 46-2005 has been reported to be effective in models of acute renal ischemia and subarachnoid hemorrhage in rats (Clozel M. , et al., "Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist," Nature, 1993;365:759) . In addition, the ET A antagonist BQ-123 has been shown to prevent early cerebral vasospasm following subarach¬ noid hemorrhage (Clozel M. and Watanabe H., Life Sci. 1993;52:825-834. Most recently an ET A selective antagonist demonstrated an oral antihypertensive effect (Stein P.D., et al., "The Discovery of Sulfonamide Endothelin Antagonists and the Development of the Orally "Active ET A Antagonist 5- (Dimethylamino) -N- (3,4- dimethyl-5-isoxazolyl) -1-naphthalenesulfonamide, " J. Med. Chem.. 1994;37:329-331. 6:605 teaches the condensation of methyl and ethyl ot-phenyl-jδ- (para-substituted)benzoylpropionates with benzaldehyde and piperonal in the presence of sodium methylate, followed by acidification, produces cyclic compounds. Allen C.F.H., Frame G.F., Normington J.B., Wilson C.V., Can. J. Research 1933;8:137 teaches the condensation of benzaldehyde with methyl and ethyl α-aryl-/S-benzoylpropionates in the presence of sodium methylate, followed by acidification, to give unsaturated ketonic acids. Allen, C.F., Normington, J.B., Wilson, C.V., Can. J. Research 1934;11:382 recites a number of highly substituted acrylic acids or their lactols. Allen, C.F.H., Davis, T.J. , Stewart, D.W., VanAllan, J.A. , Can. J. Chem. 1956;34:926 shows that a aryl-3-aroylpropionic acids exist in an open-chain configuration while the condensation products of these latter acids with aromatic aldehydes are lactols, refuting his previous article Can. J. Research 1933;8:137. Compounds of formula wherein: phenyl phenyl phenyl piperonyl (<» ,) phenyl phenyl anisyl (p-methoxyphenyl) anisyl phenyl anisyl anisyl phenyl phenyl phenyl phenyl anisyl phenyl phenyl 11/1 are all known from the above four literature references. However, the methods of using 2 (5H) -furanone, 3- (l,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (phenylmethyl) - (hereinafter Compound A) and a pharmaceutical composition containing it are new. -12- SUMMARY OF THE INVENTION The present invention includes compounds of Formula I or a pharmaceutically acceptable salt thereof wherein: R x is alkyl substituted or unsubstituted, straight, or branched, of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, phenyl substituted with from 1 to 5 substituents, naphthyl unsubstituted or substituted with from 1 to 5 substituents, or heteroaryl unsubstituted or substituted with from 1 to 5 substituents; R 2 is alkyl substituted or unsubstituted straight, or branched, of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, aryl which is unsubstituted or substituted with from 1 to 5 substituents, heteroaryl which is unsubstituted or substituted with from 1 to 3 substituents, R 3 is alkyl substituted or unsubstituted straight, or branched, of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, aryl which is unsubstituted or substituted with from 1 to 5 substituents, heteroaryl which is unsubstituted or substituted with from 1 to 3 substituents; - 13 - R 4 is hydrogen, hydroxy, halogen, SR 5 , 0R 5 wherein R 5 is alkyl or substituted alkyl of from l to 7 carbon atoms, NR 6 R 7 wherein R 6 and R 7 are each independently hydrogen, alkyl, substituted alkyl, substituted or unsubstituted phenyl, and (CH 2 ) n OR 5 wherein n is an integer of from 1 to 3; X is oxygen, S or NR 8 wherein R 8 is hydrogen, alkyl or substituted alkyl with the proviso that when R is monosubstituted phenyl and the substituent is p-methoxy, R 3 is not unsubstituted phenyl, monosubstituted phenyl, or mesityl and with the further proviso when R 2 is alkyl substituted, the substituent is not oxygen at the α-position to the furanone ring, and with the further proviso that R x and R 3 are not both alkyl or alkyl substituted in the same molecule. Preferred compounds of the instant invention are those of Formula I wherein R x is phenyl substituted with from 1 to 5 substituents, naphthyl unsubstituted or substituted with from l to 5 substituents, or heteroaryl unsubstituted or substituted with from 1 to 5 substituents; R 2 is alkyl substituted or unsubstituted straight, or branched, of from 1 to 7 carbon atoms, R 3 is aryl substituted or unsubstituted, heteroaryl substituted or unsubstituted; R 4 is hydroxy, OR 5 , or SR 5 ; X is O or S; with the proviso that when R x is monosubstituted phenyl and the substituent is p-methoxy, R 3 is not - 14 - unsubstituted phenyl, monosubstituted phenyl, or mesityl and with the further proviso that when R 2 is alkyl substituted, the substituent is not oxygen at the α-position to the furanone. Preferred compounds of the instant invention are those of Formula I wherein R x is 4-piperonyl, 3,4-dichlorophenyl, 3-methoxyphenyl, 3,5-dimethoxypheny1, or 3-methoxy-4,5-methylenedioxyphenyl R 2 is benzyl, 4-piperonylmethyl, 4-isopropylbenzyl, 1-naphthyl ethyl, 2-naphthylmethyl, 3-thiophenylmethyl, 2-thiophenylmethyl, 3,4- ichlorobenzyl, 3 (N-Me)indolylmethyl, 3,4-dimethoxybenzyl, 4-Me 2 aminobenzyl, 4-isopropylbenzyl, 4-chlorobenzyl, 4-methoxybenzyl, 4-methylbenzyl, 3-methylbenzyl, 4-isopropoxybenzyl, 4-acetamidobenzyl, 4-methylsulfonylbenzyl, 3-methyl-4-methoxybenzyl, - 15 - 3-allyloxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3-n-propoxybenzyl, 4- hiomethylbenzyl, 3-carbethoxybenzyl, 4-carbethoxybenzyl, 3-methoxybenzyl, 2-methoxybenzyl, or 3-chlorobenzyl; R 3 is phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 3-methoxyphenyl, 3-methyl-4-methoxyphenyl, 3,4-dimethoxyphenyl, or 2,4-dimethoxyphenyl; R 4 is hydroxy, OCH 3 , OCH 2 CHO, 0CH 2 C00H, OCH 2 CH(OH)CH 2 OH, or 0CH 2 (m-OH-phenyl) , and X is oxygen. More preferred compounds of the instant invention are those of Formula I wherein R x is 4-piperonyl, 3,5-dimethoxyphenyl, or 3-methoxy-4,5-methylenedioxyphenyl; R 2 is 4-piperonylmethyl, 4-isopropylbenzyl, 2- aphthylmethyl, 1-naphthylmethyl, benzyl, 2-thiophenylmethyl, - 16 - 3-thiophenylmethyl, 3- (N-Me)indolylmethyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 4-isopropoxybenzyl, 4-acetamidobenzyl, 4-methylsulfonylbenzyl, 3-methyl-4-methoxybenzyl, 3-allyloxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3-n-propoxybenzyl, 4-thiomethylbenzyl, 3-carbethoxybenzyl, 4-carbethoxybenzyl, 2-methoxybenzyl, 3-methoxybenzyl, or 3-chlorobenzyl; R 3 is 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3-methyl-4-methoxyphenyl, or 2,4-dimethoxyphenyl; R 4 is OH; and X is oxygen. Still more preferred compounds of the instant invention are selected from: 2 (5H) -furanone, 5- (4-chlorophenyl) -5-hydroxy- 3- [4- (1-methylethyl)phenyl] -4- (phenylmethyl) -, (±) -, (±) -3- (l,3-benzodioxol-5-yl) -5- (4-chlorophenyl) - 4- (phenylmethyl) -5- (2-propenyloxy) -2(5H) -furanone, acetaldehyde, [ [4- (1,3-benzodioxol-5-yl) - 2- (4-chlorophenyl) -2,5-dihydro-5-oxo-3- (phenylmethyl) 2-furanyl]oxo] -, (±) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- (2,3-dihydroxypropoxy) - 4- (phenylmethyl) -, (±) -, - 17- acetic acid, [ [4- (1,3-benzodioxol-5-yl) -2- (4-chlorophenyl) -2,5- ihydro-3- (phenylmethyl) - 5-oxo-2-furanyl]oxy] -, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- [ (3-hydroxyphenyl)methoxy] - 4- (phenylmethyl) -, (±) -, 2(5H) -furanone, 3- (1,3- enzodioxol-5-yl) - 5- (4-chlorophenyl) -5- (phenylamino) -4- (phenylmethyl) -, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- (phenylmethyl) -5- [ (phenylmethyl) - a ino]-, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methylphenyl) -4- (phenylmethyl) -, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5-phenyl-4- (phenylmethyl) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5-phenyl-4- (2-thienylmethyl) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5-phenyl-4- (3-thienylmethyl) -, 2(5H) -furanone, 5- (4-chlorophenyl) -3- (2,3-dihydro- 1,4-benzodioxin-6-yl) -5-hydroxy-4- (phenylmethyl) -, 2(5H) -furanone, 3- (l,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- [ (4-chlorophenyl)methyl] - 5-hydroxy-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- [ (4- ethoxyphenyl) - methyl] -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- ( -chlorophenyl) -5-hydroxy-4- [ (4-methylphenyl) - methyl] -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- [ (3-methylphenyl) - methyl] -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (2-thienylmethyl) -, - 18 - 2 (5H) -furanone, 5- (4-chloropheny1) -5-hydroxy- 3- [4- (1-methylethyl)phenyl] - 4- (1-naphthalenyl- methyl)-, (±)-, 2(5H) -furanone, 5- (4-chloropheny1) -5-hydroxy- 3- [4- (1-methylethyl)phenyl] -4- (2-naphthalenylmethyl) -, (±)-, 2 (5H) -furanone, 4- (1,3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -5-hydroxy-3- [4- (1-methylethyl) - phenyl]-, (±)-, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (2-naphthalenylmethyl) -, (±)-, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (1-naphthalenylmethyl) -, (±)-, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- [ [4- (1-methylethyl) - phenyl]methyl] -, (±) -, 2(5H) -furanone, 3- (1,3- enzodioxol-5-yl) - 4- (1,3-benzodioxol-5-ylmethyl) -5- (4-chlorophenyl) - 5-hydroxy-, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methoxyphenyl) -4- (phenylmethyl) -, 2 (5H) -f ranone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- [ (3-methoxy- phenyl)methyl] -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (3-thienylmethyl) -, 2(5H) -furanone, 5- (4-chlorophenyl) -3 [4- (dimethyl- amino)phenyl] -5-hydroxy-4- (phenylmethyl) -, (±) -, 2(5H) -furanone, 5- (4-chlorophenyl) - 4- [(3,4-dichlorophenyl)methyl] -3- [(4-dimethylamino) - phenyl] -5-hydroxy, (±) -, 2 (5H) -furanone, 4- (1,3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -3- [4- (dimethlamino)phenyl] - 5-hydroxy-, (±)-, - 19 - 2(5H) -furanone, 5- (4-chlorophenyl) - 3- [4- (dimethlamino)phenyl] -4- [ [4- (dimethylamino) - phenyl]methyl] -5- ydroxy-, (±) -, 2 (5H) -furanone, 5- (4-chlorophenyl) - 4- [ (3,4-dimethoxyphenyl)methyl] -3- [4- (dimethylamino) - phenyl] -5-hydroxyphenyl)methyl] -3- [4- (dimethylamino) - phenyl] -5-hydroxy-, (±) -, 2(5H) -furanone, 5- (4-chlorophenyl) - 3- [ (4- (dimethylamino)phenyl] -5-hydroxy- 4- [[4- (1-methylethyl)phenyl] ethyl] -, (±) -, 2(5H) -furanone, 5- (4-chlorophenyl) - 3- (3,4-dichlorophenyl) -5-hydroxy-4- (phenylmethyl) -, (±)-, 2(5H) -furanone, 4- (1,3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -3-)3,4-dimethoxyphenyl) -5-hydroxy, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- [(1-methyl-lH-indol- 3-yl)methyl], (±)-, 2(5H) -furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -5-hydroxy-4- (phenylmethyl) -, (± ) -, 2(5H) -furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -4- [ (3,4-dimethoxy- phenyl)methyl] -5-hydroxy-, (±)-, 2(5H) -furanone, 4- (1,3- enzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -3- (3,4-dichlorophenyl) -5-hydroxy-, (±)-, 2(5H) -furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -5-hydroxy-4- [ [4- (1-methyl- ethyl)phenyl]methyl] -, (±) -, 2(5H) -furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -4- [ [4- (dimethylamino)phenyl] - methyl] -5-hydroxy-, (±) - 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- (phenylmethyl) -5-propoxy-, (±) -, -20- 2 (5H) -furanone, 5- (4-chlorophenyl) - 4- [(3,4-dichlorophenyl)methyl] -3- (3,4-dimethoxyphenyl) • 5-hydroxy-, (±)-, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- [ (3-chlorophenyl) ethyl] - 5-hydroxy, 3-benzo[l,3]dioxol-5-yl-4- (4-tert-butyl-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- phenyl) -4- (4-methyl-benzyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4- (4-chloro-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl) -4- (3-1rifluoromethyl-benzyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4- (4-bromo-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-4- (isopropoxy- benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4- (4-dimethylamino- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4- (4-benzyloxy-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzo[1,3]dioxol- 5-ylmethyl-5-hydroxy-5- (4-methoxy-phenyl) -5H-furan- 2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl) -4- (4-trifluoromethyl-benzyl) -5H-furan-2-one, 3- enzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-methoxy- 3-methyl-benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl) -4- (3-methyl-benzyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4-ethyl-5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3-Benzo[2,3]dioxol-5-yl-4- (3-chloro-4-methoxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, -21 - 3-benzo[l,3]dioxol-5-yl-4- (4-butoxy-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (4-chloro-phenyl) -5-hydroxy-4- (4-methoxy¬ benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 5-hydroxy-4- (4-methoxy-benzyl) -3,5-bis- (4-methoxy- phenyl) -5H-furan-2-one, 5-hydroxy-4- (4-methoxy-benzyl) -5- (4-methoxy- phenyl) -3-p-tolyl-5H-furan-2-one, 5-hydroxy-4- (4-methoxy-benzyl) -5- (4-methoxy- phenyl) -3-phenyl-5H-furan-2-one, 4-benzyl-3- (2,4-dimethox -phenyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,4-dichloro-phenyi) -5-hydroxy-4- (4-methoxy¬ benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 5- (4-chloro-phenyl) -3- (3,4-dichloro-phenyl) - 5-hydroxy-4- (4-isopropyl-benzyl) -5H-furan-2-one, 5- (4-chloro-phenyl) -3- (3,4-dichloro-phenyl) - 4- (4-dimethylamino-benzyl) -5-hydroxy-5H-furan-2-one, 4-benzyl-3- (3,4-dichloro-phenyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,4-dichloro-phenyl) -5-hydroxy-4- (4-isopropyl- benzyl) -5- ( -methoxy-phenyl) -5H-furan-2-one, 4-benzyl-3- (3,5-dimethoxy-phenyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,5-dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy- phenyl) -4- (3-propoxy-benzyl) -5H-furan-2-one, 4- (3-chlo o-benzyl) -3- (3,5-dimethoxy-phenyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,5-dimethoxy-phenyl)-5-hydroxy-5- (4-methoxy- phenyl) -4- (3-trifluoromethyl-benzyl) -5H-furan-2-one, 3- (3,5-dimethoxy-phenyl) -4- (3-fluoro-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,5-dimethoxy-phenyl) -5-hydroxy-4- (3-methoxy- benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,5-dimethoxy-phenyl) -5-hydroxy-4- (4-methoxy- benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, -22 - 4- (3,5-dichloro-benzyl) -3- (3,5-dimethox -phenyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,5-dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy¬ phenyl) -4-pyridin-3-ylmethyl-5H-furan-2-one, 3- [4- (3,5-dimethoxy-phenyl) -2-hydroxy- 2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -benzaldehyde, 4- (3-allyloxy-4-methoxy-benzyl) -3- (3,5-dimethoxy¬ phenyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 4-benzyl-5-hydroxy-5- (4-methoxy-phenyl) - 3- (2,3,4,5,6-pentafluoro-phenyl) -5H-furan-2-one, 4-benzyl-3- (3,4-difluoro-phenyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,4-difluoro-phenyl) -5-hydroxy-4- (4-isopropyl- benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 3- (3,4-difluoro-phenyl) -4- (4-dimethylamino- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 4-benzyl-3- (3,5-dichloro-phenyl) -5-hydroxy- 5- (4-Tmethoxy-phenyl) -5H-furan-2-one, 4-benzyl-5-hydroxy-5- (4-methoxy-phenyl) - 3- (3-methoxy-phenyl) -5H-furan-2-one, 5-hydroxy-5- (4-methoxy-phenyl) -3- (3-methoxy¬ phenyl) -4- (3-propoxy-benzyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4-benzyl-5- (2,6-difluoro- phenyl) -5-hydroxy-5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl) -4- (3-propoxy-benzyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- phenyl) -4-pyridin-3-ylmethyl-5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-4-isoquinolin- 4-ylmethyl-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-biphenyl-4-ylmethyl- 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 4- (3-allyloxy-4-methoxy-benzyl) -3-benzo[l,3] - dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) -5H-furan- 2-one, -23 - 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-4- (4-isoquinolinyl) -5- (4-methoxyphenyl) -, (±) -, monohydrochloride, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methoxyphenyl) -4- (3-pyridinylmethyl) -, (±) -, monohydrochloride, 2(5H) -furanone, 3- (3,5-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -4- (3-pyridinylmethyl) -, (±) -, monohydrochloride, 4-benzyl-5-hydroxy-5- (4-methoxy-phenyl) - 3- (1-methyl) -1H-indol-3-yl) -5H-furan-2-one, 2-butenoic acid, 2- (1,3-benzodioxol-5-yl) - 4- (4-methoxyphenyl) -4-oxo-3- (phenylmethyl) -, (Z) -, ion(l-) compd. with 2-hydroxy-N,N,N-triethanaminium (1:1), 2-butenoic acid, 2- (1,3-benzodioxol-4-yl) -3- [ (4-methoxy-3-methylphenyl)methyl] -4- (4-methoxyphenyl) - 4-oxo, (Z)-, ion(l-) compound with 2-hydroxy-N,N,N- trimethylethanaminum (1:1) , 2-butenoic acid, 2- (1,3-benzodioxol-5-yl)-4- (4-methoxyphenyl) -4-oxo-3- [[4- (trifluoromethyl)phenyl] - methyl]-, (Z)-, ion(l-) compound with 2-hydroxy-N,N,N- trimethylethanaminium 1:1), 4'-benzyl-5' -hydroxy-5'- (4-methoxy-phenyl) - 5'H- [2,3']bifuranyl-2'-one, 4-benzyl-5-hydroxy-5- (4-methoxy-phenyl) - 3- hiophen-2-yl-5H-furan-2-one, 4-benzyl-5-hydroxy-5- (4-methoxy-phenyl) -5H- [3,3']bifuranyl-2-one, 3-benzo[l,3]dioxol-5-yl-4-benzyl-5- (3,4-dimethoxy¬ phenyl) -5-hydroxy-5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5- (3,4-dichloro- phenyl) -5-hydroxy-5H-furan-2-one, 4- (4-benzo[l,3]dioxol-5-yl-3-benzyl-2-hydroxy- 5-oxo-2,5-dihydro-furan-2-yl) -benzoic acid methyl ester, -24- 4- [4-benzo[l,3]dioxol-5-yl-3-benzyl-2-hydroxy- 5-oxo-2,5-dihydro-furan-2-yl) -benzoic acid, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5- (4-isopropyl- phenyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4-benzyl-5- (4-benzyloxy- pheny1) -5-hydroxy-5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5- (3,4-dimethyl- phenyl) -5-hydroxy-5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5-o-tolyl-5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5- (3-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-cyclohexylmethyl- 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5-methoxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5- (4-methoxy¬ phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5-m-tolyl-5H-furan-2-one, 4-benzyl-5-hydroxy-5- (4-methoxy-phenyl) - 3- (3,4,5-trimethoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5- (3-chloro- phenyl) -5-hydroxy-5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- phenyl) -4- (4-methylsulfanyl-benzyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-methane- sulfonyl-benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4-benzyl-5- (2,4-dimethoxy- phenyl) -5-hydroxy-5H-furan-2-one, 3,4-bis-benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5- (2-methoxy-phenyl)-5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- phenyl) -4-naphthalen-1-ylmethyl-5H-furan-2-one, -25 - 3-benzo[l,3]dioxol-5-yl-5-hydroxy-4- (4-methoxy- 2,5-dime hyl-benzyl) -5- (4-methoxy-phenyl) -5H-furan- 2-one, [R-(R*,S*)] and [S- (R*,R*) ]carbamic acid, (1-phenylethyl) -, 4- (1,3-benzodioxol-5-yl) -2,5-dihydro- 2- (4-methyoxyphenyl) -5-oxo-3- (phenylmethyl) -2-furanyl ester, 2-butenoic acid, 2- (1,3-benzodioxol-5-yl) -4- (4- methoxyphenyl) -4-oxo-3- [(3-propoxyphenyl)methyl] -, (Z)-, ion(l-) compd. with 2-hydroxy-N,N,N-trimethyi- ethanaminium (1:1) , 3-benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-methoxy- 2,3-dimethyl-benzyl) -5- (4-methoxy-phenyl) -5H-furan- 2-one, 4- (3-allyloxy-4-methoxy-benzyl) -3-benzo[1,3] - dioxol-5-yl-5-(2,4-dimethoxy-phenyl) -5-hydroxy-5H- furan-2-one, 3-benzo[l,3]dioxol-5-yl-4-benzyl-5- (4-chloro- pheny1) -5-hydroxy-1,5-dihydro-pyrrol-2-one, 3-benzo[l,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- phenyl) -4- (2-phenoxybenzyl) -5H-furan-2-one, 4-benzyl-3- (3,4-dimethoxy-phenyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 2H-pyrrole-2-one, 3- (1,3-benzodioxol-5-yl) -1,5- dihydro-5-hydroxy-4,5-bis(4-methoxyphenyl) -, (±) -, 3-benzo[i,3]dioxol-5-yl-4-benzyl-5- (4-ethyl- pheny1) -5-hydroxy-5H-furan-2-one, 3- [4- (3,5-dimethoxy-phenyl) -2-hydroxy-2- (4- methoxy-phenyl) -5-oxo-2,5-dihydro-furan-3ylmethyl] - benzoic acid 4- [4-benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy¬ phenyl) -5-oxo-2,5-dihydro-furan-3-ylmethyl] -benzoic acid, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- (4-methoxy- 3-methylbenzyl) -5- ( -methoxyphenyl) -5H-furan-2-one, -26 - 3- (3,5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- phenyl) -4- (4-methylbenzyl) -5H-furan-2-one, 4- (4-Chlorobenzyl) -3- (3,5-dimethoxyphenyl) - 5-hydroxy-5- (4- ethoxyphenyl) -5H-furan-2-one, 5 2 (5H) -Furanone, 4- (cyclohexylmethyl) -3- (3,5-dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - , 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- (2-methoxy- benzyl) -5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- 0 phenyl) -4- (2-methylbenzyl) -5H-furan-2-one, 4- (2-Chlorobenzyl) -3- (3,5-dimethoxyphenyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 4- (4-Benzo[l,3]dioxol-5-yl-2-hydroxy- 2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran- 5 3-ylmethyl]benzoic acid, l,3-Benzodioxol-5-acetic acid, a- [2- [ (4-carboxyphenyl)methyl] -2- (4-methoxybenzoyl) - ethylidene] - , disodium salt, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- 0 phenyl) -4- (3,4,5-trimethoxy-benzyl) -5H-furan-2-one, 3-benzo[l,3]dioxol-5-yl-4- (2-chloro-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl) -4- (2-methyl-benzyl) -5H-furan-2-one, 5 3-benzo[l,3]dioxol-5-yl-5-hydroxy-4- (2-methoxy- benzyl-5- (4-methyoxy-phenyl) -5H-furan-2-one, 3-benzo[1,3]dioxol-5-yl-5-hydroxy-4,5-bis- ~t ^ ^ (4-methoxyphenyl) -5H-furan-2-one, Benzoic acid, 3- [ [4- (1,3-benzodioxol-5-yl) - 0 2,5-dihydro-2-hydroxy-2- (4-methoxyphenyl) -5-oxo- 3-furanyl]methyl] - , methyl ester 2 (5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methoxy-3-methylphenyl) -4- (phenyl¬ methyl)-, (+/-)-, -27- {4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy- 2- (4-methoxyphenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -phenyl}-acetic acid methyl ester, {3- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy- 2- (4-methoxyphenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl]phenyl}-acetic acid methyl ester, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-methoxy- 3,5-dimethyl-benzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 4-Benzyl-5-hydroxy-3- (7-methoxybenzo[1,3]dioxol- 5-yl) -5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (3,5-dimethoxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (3,4-dimethoxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- phenyl) -4- (2,3,4-trimethoxybenzyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl) -4- (2,4,5-trimethoxybenzyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (2,5-dimethoxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (2,3-dimethoxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (4-benzyloxy-3-methoxy- benzyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-cyclopentylmethyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 4H-Naphtho[2,3-Jb]pyran-4-one, 2- (3-hydroxy- 4-methoxyphenyl) -, 3-Benzo[1,3] ioxol-5-yl-4-cyclohex-3-enylmethyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-(2-cyclopentyl-2-phenyl ■ ethyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- [2- (benzo[1,3]dioxol- 5-yloxy) -benzyl] -5-hydroxy-5- (4-methoxyphenyl) -5H- -furan-2-one, -28 - 4- (2-Allyloxy-4-methoxybenzyl) -3-benzo[1,3]dioxol- 5-yl-5-hydroxy-5- (4- ethoxyphenyl) -5H-furan-2-one, Sodium 2-benzo[1,3]dioxol-5-yl-3-benzyl-4- (4-methoxyphenyl) -4-oxo-but-2-enoate, 1,3-Benzodioxol-5-acetic acid, α- [2- (4-methoxy¬ phenyl) -1- [ [4- (1-methylethoxy)phenyl]methyl] - 2-oxoethylene] -, (Z)-, choline salt, Sodium 2-benzo[l,3]dioxol-5-yl-3- (4-isopropoxy- benzyl) -4- (4-methoxyphenyl) -4-oxo-but-2-enoate, Sodium 2-Benzo[l,3]dioxol-5-yl-3-benzyl-4- (4-methoxy-3-methylphenyl) -4-oxo-but-2-enoate PD 157779 - E356 5-Hydroxy-3- (7-methoxybenzo[1,3]dioxol-5-yl) - 5- (4-methoxyphenyl) -4- (3,4,5-trimethoxybenzyl) -5H-furan -2-one, 4-Benzyl-5-hydroxy-3- (7-methoxy-benzo[1,3]dioxol- 5-yl) -5- (4-methoxy-3-methylphenyl) -5H-furan-2-one, 5-Hydroxy-3- (7-methoxy-benzo[l,3]dioxol-5-yl) - 5- (4-methoxy-3-methyl-phenyl) -4- (3,4,5-trimethoxy- benzyl) -5H-furan-2-one, {4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxyphenyl) -5-oxo-2,5-dihydro-furan-3-ylmethyl] - 2,6-dimethoxyphenoxy}-acetic acid ethyl ester, {5- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4- ethoxyphenyl) -5-oxo-2,5-dihydro-furan-3-ylmethyl] - 2,3-dimethoxyphenoxy}-acetic acid ethyl ester, {5- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran-3-ylmethyl] - 2,3-dimethoxyphenoxy}-acetic acid, {5- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran-3-ylmethyl] - 2,3-dimethoxyphenoxy}-acetic acid, Potassiuin 3- (4-acetylamino-benzyl) - 2-benzo[l,3]dioxol-5-yl-4- (4-methoxy-phenyl) -4-oxobut- 2-enoate. - 29 - Sodiu 2-benzo[l,3]dioxol-5-yl-3- (4-methoxy- benzoyl) -4- (4-methoxy-2,5-dimethylphenyl)but-2-enoate, Sodium 3-benzyl-2- (7-methoxybenzo[1,3]dioxol- 5-yl) -4- (4-methoxyphenyl) -4-oxo-but-2-enoate, Sodium 2- (7-methoxybenzo- [1,3]dioxol-5-yl) -3- (4-methoxy-3-methylbenzoyl-4- (3,4,5-trimethoxyphenyl) - but-2-enoate, Sodium 3-benzyl-2- (7-methoxybenzo[1,3]dioxol- 5-yl) -4- (4-methoxy-3-methylphenyl) -4-oxobut-2-enoate, Sodium 2- (7-methoxybenzo- [1,3]dioxol-5-yl) -4- (4-methoxyphenyl) -4-oxo-3- (3,4,5-trimethoxybenzyl) -but ■ 2-enoate, Sodium 2- (7-methoxybenzo- [1,3]dioxol-5-yl) -4- (4- ethoxyphenyl) -4-oxo-3- (3,4,5-trimethoxybenzyl) -but■ 2-enoate, Sodium 3-cyclohexylmethyl-2- (3,5-dimethoxyphenyl) ■ 4- (4-methoxyphenyl) -4-oxobut-2-enoate, Sodium 2-Benzo[l,3]dioxol-5-yl-3- (4-methoxy- benzyl) -4- (4-methoxyphenyl) -4-oxobut-2-enoate, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (3-methoxy- 4-octyloxybenzyl) -5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- 3-methylphenyl) -4- (3,4,5-trimethoxybenzyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy- 3-methylphenyl) -4- (3,4,5-trimethoxybenzyl) -5H-furan- -2-one, N-{4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-3-methylphenyl) -5-oxo-2,5-dihydrofuran- 3-ylmethyl] -phenyl}-acetamide, N-{4- [4- (3,5-Dimethoxyphenyl) -2-hydroxy-2- (4-methoxy-3-methylphenyl) -5-oxo-2,5-dihydrofuran- 3-ylmethyl]phenyl}-acetamide, Potassium 3- (4-acetylaminobenzyl) -2- (3,5-dimethoxyphenyl) -4- (4-methoxy-3-methylphenyl) - 4-oxobut-2-enoate, - 30 - Sodium 2-Benzo[1,3]dioxol-5-yl-4- (4-methoxy- 3-methyl-phenyl) -4-oxo-3- (3,4,5-trimethoxy-benzyl) -but- 2-enoate, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- phenyl) -4- (3,4,5-trimethoxybenzyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- (4-isopropoxy- 3-methoxybenzyl) -5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- (4-isopropoxy- 3-methoxybenzyl) -5- (4-methoxy-3-methylphenyl) -5H-furan- 2-one 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-isopropoxy- 3-methoxybenzyl) -5- (4-methoxy-3-methylphenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-isopropoxy- 3-methylbenzyl) -5- (4-methoxy-3-methylphenyl) -5H-furan- 2-one, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (4-isopro- poxy-3-methyl-benzyl) -5- (4-methoxy-3-methyl-phenyl) - 5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (4-cyclohexyloxy- 3-methyl-benzyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy¬ phenyl)-4-(l,2,3,4-tetrahydro-naphthalen-1-ylmethyl) - 5H-furan-2-one, 3- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2,5-dihydrofuran-3-ylmethyl]cyclohexane- carboxylic acid methyl ester, 3-Benzo[1,3]dioxol-5-yl-4-cyclopropylmethyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 1,3-Benzodioxol-5-acetic acid, α;- [1- [ [3- (methoxy- carbonyl)phenyl]methyl] -2- (4-methoxyphenyl) - 2-oxoethylene] -, monopotassium salt, 4-Benzyl-3- (2,5-dimethoxy-phenyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, -SI¬ S' (2,5-Dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy- phenyl) -4- (3,4,5-trimethoxy-benzyl) -5H-furan-2-one, 3- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2,5-dihydro-furan-3-ylmethyl] - cyclohexanecarboxylic acid, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-isopropyl- benzyl) -5- (4-methoxy-phenyl) -5g-furan-2-one, or 2-Benzo[l,3]dioxol-5-yl-3- (4-methoxybenzoyl) -4- (2-methoxyphenyl) -but-2-enoic acid. Elevated levels of endothelin have been postulated to be involved in a number of pathophysiological states including diseases associated with the cardiovascular system as well as various metabolic and endocrinological disorders. As antagonists of endothelin, the compounds of Formula I are useful in the treatment of hypertension, myocardial infarction, diabetes, cerebral vasospasm, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, chronic and acute renal failure, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, stroke, head injury, and ischemic bowel disease. The compound of Formula 1A wherein R x is piperonyl, R 2 is benzyl, and R 4 is p-chlorophenyl will also be useful in the above treatments. (See Allen references cited hereinbefore.) A still further embodiment of the present invention is a pharmaceutical composition for administering a therapeutically effective amount of a compound of Formula I in unit dosage form in the treatment methods mentioned above. Finally, the present invention is directed to methods for production of a compound of Formula I. -32- DETAILED DESCRIPTION OF THE INVENTION In the compounds of Formula I, the term "alkyl" means a straight or branched hydrocarbon radical having from 1 to 12 carbon atoms unless otherwise specified and includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, allyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, and dodecyl. The alkyl group is unsubstituted or substituted by from 1 to 3 substituents selected from alkyl, alkoxy, thioalkoxy all as defined herein, hydroxy, thiol, nitro, halogen, amino, formyl, 0 0 0 carboxyl, nitrile, -NH-C-alkyl, -C-NH-alkyl, -C-O-alkyl, 0 -C-alkyl, aryl, or heteroaryl wherein alkyl, aryl, and heteroaryl are defined as herein. The term "cycloalkyl" means a saturated hydrocarbon ring which contains from 3 to 12 carbon atoms unless otherwise specified, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and adamantyl. The cycloalkyl ring may be unsubstituted or substituted by from 1 to 3 substituents selected from alkyl, cycloalkyl, cycloalkoxy, alkoxy, thioalkoxy all as defined herein, hydroxy, thiol, nitro, halogen, amino, formyl, carboxyl, nitrile, alkylsulfoxyl, arylsulfoxyl, alkylsulfonyl, arylsulfonyl, 0 0 0 0 II II II II -NH-C-alkyl, -C-NH-alkyl, -C-O-alkyl, -C-alkyl, aryl, or heteroaryl wherein alkyl, aryl, and heteroaryl are defined as herein. The terms "alkoxy" and "thioalkoxy" are 0-alkyl or S-alkyl as defined above for alkyl. - 33 - The term "aryl" means an aromatic radical which is a phenyl group, a benzyl group, a naphthyl group, a biphenyl group, a pyrenyl group, an anthracenyl group, or a fluorenyl group and the like, unsubstituted or substituted by 1 to 3 substituents selected from alkyl as defined above, alkoxy as defined above, thioalkoxy as defined above, hydroxy, thiol, nitro, halogen, amino, formyl, carboxy, nitrile, arylsulfoxyl, alkylsulfoxyl, arylsulfonyl, alkylsulfonyl, 0 0 0 0 -NH-C-alkyl, -C-NH-alkyl, -C-O-alkyl, -C-alkyl, aryl, or heteroaryl wherein alkyl, aryl, and heteroaryl are defined as above. The term "heteroaryl" means a heteroaromatic radical which is 2-or 3-thienyl, 2- or 3-furanyl, 2- or 3-pyrrolyl, 2-, 4-, or 5-imidazolyl, 3-, 4-, or 5-pyrazolyl, 2-, 4-, or 5-thiazolyl, 3-, 4-, or 5-isothiazolyl, 2-, 4-, or 5-oxazolyl, 3-, 4-, or 5-isoxazolyl, 3- or 5-1,2,4-triazolyl, 4- or 5-1,2,3-triazolyl, tetrazolyl, 2-, 3-, or 4-pyridinyl, 3-, 4-, or 5-pyridazinyl, 2-pyrazinyl, 2-, 4-, or 5-pyrimidinyl, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolinyl, 1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolinyl, 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 2-, 3-, 4-, 5-, 6-, or 7-benzo[b]thienyl, or 2-, 4-, 5-, 6-, or 7-benzoxazolyl, 2-, 4-, 5-, 6-, or 7-benzimidazolyl, 2-, 4-, 5-, 6-, or 7-benzothiazolyl, unsubstituted or substituted by 1 to 3 substituents selected from alkyl as defined above, aryl as defined above, alkoxy as defined above, thioalkoxy as defined above, hydroxy, thiol, nitro, halogen, formyl, amino, carboxyl, 0 0 0 II II II nitrile, -NH-C-alkyl, -C-O-alkyl, -C-alkyl wherein alkyl is as defined above or phenyl. "Halogen" is fluorine, chlorine, bromine or iodine. - 34 - So e of the compounds of Formula I are capable of further forming both pharmaceutically acceptable acid addition and/or base salts. All of these forms are within the scope of the present invention. Pharmaceutically acceptable acid addition salts of the compounds of Formula I include salts derived from nontoxic inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydriodic, hydrofluoric, phosphorous, and the like, as well as the salts derived from nontoxic organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl- substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc. Such salts thus include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, methanesulfonate, and the like. Also contemplated are salts of amino acids such as arginate and the like and gluconate, galacturonate (see, for example, Berge, S.M., et al., "Pharmaceutical Salts, " Journal of Pharmaceutical Science 1977;66:1-19) . The acid addition salts of said basic compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt in the conventional manner. Pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Examples - 35 - of metals used as cations are sodium, potassium, magnesium, calcium, and the like. Examples of suitable amines are N,N' -dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge, S.M. , et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science 1977;66:1-19). The base addition salts of said acidic compounds are prepared by contacting the free acid form with a sufficient amount of the desired base to produce the salt in the conventional manner. Certain of the compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms, including hydrated forms, are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present invention. Certain of the compounds of the present invention possess one or more chiral centers and each center may exist in the R(D) or S(L) configuration. The present invention includes all enantiomeric and epimeric forms as well as the appropriate mixtures thereof. In addition, some of the cyclic lactones of Formula I and Compound A may exist in a tautomeric open chain keto- acid form, Formula II below, depending on the substitution pattern present at R x , R 2 , and R 3 , or pH. In such cases, the rate of equilibration may vary and activity may thus reside with either tautomer. The compounds of Formula I and Compound A are valuable antagonists of endothelin. The tests employed - 36 - indicate that compounds of the invention possess endothelin antagonist activity. Thus, the compounds were tested for their ability to inhibit [ 125 I] -ET-K [ 125 I] -Endothelin-1) binding in a receptor assay. Selected compounds were also tested for antagonist activity by inhibition of ET-1 stimulated arachidonic acid release and ET-1 stimulated vasoconstriction. The following testing procedures were used (Doherty, A.M., et al., "Design of C-Terminal Peptide Antagonists of Endothelin: Structure-Activity Relationships of ET-1 [16-21, D-His 16 ]", Bioorganic and Medicinal Chemistry Letters 1993;3:497-502). ENDOTHELIN RECEPTOR BINDING ASSAY-A (ERBA-A) INTACT CELL BINDING OF [ 125 I] -ET-1 Materials and Terms Used: Cells The cells used were rabbit renal artery vascular smooth muscle cells grown in a 48-well dish (1 cm 2 ) (confluent cells) . Growth Media The growth media was Dulbecco's Modified Eagles/Ham's F12 which contained 10% fetal bovine serum and antibiotics (penicillin/streptomycin/fungizone) . Assay Buffer The assay buffer was a medium 199 containing Hanks salts and 25 mM Hepes buffer (Gibco 380-2350AJ) , supplemented with penicillin/streptomycin/fungizone (0.5%) and bovine serum albumin (1 mg/mL) . [ 125 I] -ET-1 Amersham radioiodinated endothelin-1 [ 125 I] -ET-1 was used at final concentration of 20,000 cpm/0.25 mL (25 pM) . -37- Protocol First, add 0.5 mL warm assay buffer (described above) to the aspirated growth media and preincubate for 2 to 3 hours in a 37°C water bath (do not put back in the 5% carbon dioxide) . Second, remove the assay buffers, place the dish on ice, and add 150 μL of cold assay buffer described above to each well. Third, add 50 mL each of cold [ 125 I] -ET-1 and competing ligand to the solution (at the same time if possible) . Next, place dish in a 37°C water bath for about 2 hours and gently agitate the dish every 15 minutes. Discard the radioactive incubation mixture in the sink and wash wells 3 times with 1 mL of cold phosphate buffered saline. Last, add 250 mL of 0.25 molar sodium hydroxide, agitate for 1 hour on a rotator, and then transfer the sodium hydroxide extract to gamma counting tubes and count the radioactivity. ENDOTHELIN RECEPTOR BINDING ASSAY-B (ERBA-B) [ 125 I]-ET-1 BINDING IN RAT CEREBELLAR MEMBRANES Materials and Terms Used: Tissue Buffer The tissue is made up of 20 mM tris(hydroxy- methyl)aminomethane hydrochloride (Trizma) buffer, 2 mM ethylenediaminetetra acetate, 100 μM phenylmethylsulfonyl fluoride. Tissue Preparation First, thaw one aliquot of frozen rat cerebellar membranes (2 mg protein in 0.5 mL) . Next, add 0.5 mL membrane aliquot to 4.5 mL cold tissue buffer, polytron at 7,500 revolutions per minute for 10 seconds. Finally, dilute tissue suspension 1/100 (0.1 mL suspension + 9.9 mL tissue buffer), polytron again, and place ice. -38- Dilution Buffer Medium 199 with Hank's salts plus 25 mM Hepes + 1 mg/mL bovine serum albumin. [ 125 I] -ET-1 Amersham [ 125 I] -ET-1 (aliquots of 2 x 10 6 cp per 100 mL aliquot of [ 125 I] -ET-1 with 5.2 mL dilution buffer, place on ice until use (final concentration will be 20,000 cpm per tube, or 25 pM) . Protocol Add 50 μL each of cold [ 125 ]-ET-1 and competing ligand to tubes on ice. Mix in 150 μL of tissue to each tube, vortex briefly, then tap to force all liquids to bottom (total assay volume = 250 μL) . Then place the tubes in a 37°C water bath for 2 hours. Add 2.5 mL cold wash buffer (50 mM Trizma buffer) to each tube, filter, and then wash tube with additional 2.5 mL wash buffer and add to filter. Finally, wash filters with an additional 2.5 mL of cold wash buffer. Count filters for radioactivity in gamma counter. The above process has also been modified by using human recombinant CHO-Kl cells. The tissue used for human ETB was recombinant human ETB receptor expressed in CHO-Kl cells (Chinese hamster ovary cells) . The gene for human ETB receptor was cloned and inserted into the pRc-CMW expression vector, then transfected into CHO-Kl cells by electroporation. For binding assays, membranes (0.7 mg protein) of CHO-Kl cells expressing recombinant human ETB receptor were used. - 39 - IN VITRO INHIBITION OF ET-1 STIMULATED ARACHIDONIC ACID RELEASE (AAR) IN CULTURED RABBIT VASCULAR SMOOTH MUSCLE CELLS (ET A ) BY THE COMPOUNDS OF THE INVENTION Antagonist activity is measured by the ability of added compounds to reduce endothelin-stimulated arachidonic acid release in cultured vascular smooth muscle cells as arachidonic acid release (AAR) . [ 3 H] Arachidonic Acid Loading Media (LM) is DME/F12 + 0.5% FCS x 0.25 mCi/mL [ 3 H] arachidonic acid (Amersham) . Confluent monolayers of cultured rabbit renal artery vascular smooth muscle cells were incubated in 0.5 mL of the LM over 18 hours, at 37°C, in 5% C0 2 . The LM was aspirated and the cells were washed once with the assay buffer (Hank's BSS + 10 mM HEPES + fatty acid-free BSA (1 mg/mL) ) , and incubated for 5 minutes with 1 mL of the prewarmed assay buffer. This solution was aspirated, followed by an additional 1 mL of prewarmed assay buffer, and further incubated for another 5 minutes. A final 5-minute incubation was carried out in a similar manner. The same procedure was repeated with the inclusion of 10 μL of the test compound (1 nM to 1 μM) and 10 μL ET-1 (0.3 nM) and the incubation was extended for 30 minutes. This solution was then collected, 10 μL of scintillation cocktail was added, and the amount of [ 3 H] arachidonic acid was determined in a liquid scintillation counter. -40- IN VITRO ANTAGONISM OF ET-1 STIMULATED VASOCONSTRICTION (VERA-A) IN THE RABBIT FEMORAL ARTERY (ET λ ) AND SARAFOTOXIN 6c STIMULATED VASOCONSTRICTION IN THE RABBIT PULMONARY ARTERY (ET B ) Male New Zealand rabbits were killed by cervical dislocation and exsanguination. Femoral and pulmonary arteries were isolated, cleaned of connective tissue, and cut into 4-mm rings. The endothelium was denuded by placing the rings over hypodermic tubing (32 gauge for femoral rings and 28 gauge for pulmonary rings, Small Parts, Inc, Miami, Florida) and gently rolling them. Denuded rings were mounted in 20 mL organ baths containing Krebs-bicarbonate buffer (composition in mM: NaCl, 118.2; NaHC0 3 , 24.8; KC1, 4.6; MgS0 4 7-H 2 0, 1.2; KH 2 P0 4 , 1.2; CaCl 2 -2H 2 0; Ca-Na 2 EDTA, 0.026; dextrose, 10.0) , that was maintained at 37°C and gassed continuously with 5% C0 2 in oxygen (pH 7.4) . Resting tension was adjusted to 3.0 g for femoral and 4.0 g pulmonary arteries; the rings were left for 90 minutes to equilibrate. Vascular rings were tested for lack of functional endothelium (i.e., lack of an endothelium- dependent relaxation response to carbachol (1.0 μM.) in norepinephrine (0.03 μM) contracted rings. Agonist peptides, ET-1 (femoral) , and S6c (pulmonary) , were cumulatively added at 10-minute intervals. The ET antagonists were added 30 minutes prior to adding the agonist and pA 2 values were calculated (Table II) . The data in Table II below show the endothelin receptor binding and antagonist activity of representative compounds of the instant invention. -41- TABLE II Example ERBA-A a ERBA-B AAR-A C VERA-A b 0.15 6.4 3.8 • 42- • 43- TABLE II (cont'd) •44- TABLE II (cont'd) AAR-A C VERA-A b 6.5 6.2 6.2 6.1 7.0 6.7 7.7 7.0 -45- TABLE II (cont'd) -46- TABLE II (cont'd) a IC 50 values in μ or % inhibitor at 10 "5 M b pA2 values c μM Human cloned receptor data As can be seen in Table II above, the compounds of Formula I bind to the endothelin receptors ET A (ERBA-A) and ET B (ERBA-B) in the μM to nM range. -47- IN VIVO STUDIES Relative potencies of 171 and 253 at inhibiting ET-1 (1.0 nmol/kg, IV bolus) induced depressor and pressor responses were determined in anesthetized (Inactin 120 mg/kg, IP) , ganglionic blocked rats (male 300-500 g, Sprague Dawley) . Antagonists were administered IV bolus (3, 10, 30, 100 μmol/kg, IV bolus) in separate groups of rats (5 minutes before ET—1 challenge [see Haleen, et al., J. Cardiovasc. Pharm.. 22 (Suppl. 8) :598-5102 (1993)]). Duration of action of the antagonist was determined in conscious, chronically prepared normotensive rats. Rats were challenged with ET-1 (1.0 nmol/kg, IV bolus) on 5 consecutive days; Day 1 control and on Days 2-5 at 5, 20, 60, and 120 minutes following treatment with the antagonist. Separate groups of rats were used for each antagonist treatment. The results are shown in Table III. The said compounds also reduce endothelin- stimulated arachoidonic acid release (AAR) and therefore are antagonists. Furthermore, in vitro activity is demonstrated by the antagonism of endothelin-stimulated vasoconstric- tion of rabbit femoral artery. -48- GENERAL SYNTHETIC APPROACHES The compounds of Formula I and Compound A may be prepared by several methods. In Scheme I, condensation of an aldehyde with an acetophenone-type compound in basic solution such as alcoholic sodium hydroxide. This gives a chalcone derivative which is treated with HCN in a solvent such as aqueous alcohol to give the nitrile. The nitrile is hydrolyzed to the ester with an acidic solution such as HCl/MeOH/H 2 0. The ester is then condensed and cyclized with another aldehyde in a solvent such as methanol using a base such as sodium methoxide. Further derivatization of the alcohol can be made by chlorination of the hydroxyl with a chlorinating agent such as S0C1 2 . Even further derivatization can be accomplished with displacement of the chloride with nucleophiles, such as alcohols, other halogens, amines, and thiols. In Scheme II condensation of the anion of a . substituted acetonitrile with a benzil derivative in an organic solvent such as tetrahydrofuran and DMSO gives a compound of Formula I. In Scheme III the chalcone from Scheme I is treated with the anion of triphenylorthothioformate in an organic solvent such as THF. This compound is then converted to a keto ester with a mix of mercury salts by warming in an alcoholic solvent such as ethanol. The keto ester can then be converted to compound, of Formula I and Compound A as in Scheme I. R is H or R 2 -50- SCHEME II 10 15 20 25 30 35 -51- SCHEME III 0 2 Et - 52 - The compounds of the present invention can be prepared and administered in a wide variety of oral and parenteral dosage forms. Thus, the compounds of the present invention can be administered by injection, that is, intravenously, intramuscularly, intra- cutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the compounds of the present invention can be administered by inhalation, for example, intranasally. Additionally, the compounds of the present invention can be administered transder ally. It will be obvious to those skilled in the art that the following dosage forms may comprise as the active component, either a compound of Formula I or a corresponding pharmaceutically acceptable salt of a compound of Formula I. For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material. In powders, the carrier is a finely divided solid which is in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain from five or ten to about seventy percent of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, -53 - sodiu carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term "preparation" is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration. For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogenous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify. Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water propylene glycol solutions. For parenteral injection liquid preparations can be formulated in solution in aqueous polyethylene glycol solution. Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizing and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and -54 - emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsules, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form. The quantity of active component in a unit dose preparation may be varied or adjusted from 0.1 mg to 100 mg preferably 0.5 mg to 100 mg according to the particular application and the potency of the active component. The composition can, if desired, also contain other compatible therapeutic agents. In therapeutic use as antagonists of endothelin, the compounds utilized in the pharmaceutical method of this invention are administered at the initial dosage of about 0.01 mg to about 100 mg/kg daily. A daily dose range of about 0.01 mg to about 10 mg/kg is preferred. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the art. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the -55- circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired. The following nonlimiting examples illustrate the preferred methods for preparing the compounds of the invention. Examples 1-3, 5, 13-15, 17-19, 21-23, 27-29, 36-38, 49-51, 58-60, 62-64, 94-96, 98-100, 102-104, 106-108, 110-112, 114-116, 122-124, 136-138, 140-142, 146-148, 150-152, 155-157, 167-169, 174-176, 178-180, 183-185, 187-189, 191-193, 195-197, 200-203, 205-207, 209-211, 213-215, 217-219, 224-226, 228-230, 232-234, 238-240, 242-244, 246-248, 258-260, 263-265, 268-270, 287-289, 298-300, 311-312, 317-318, 320-321, 323, 325-328, 331-332, 334-336, 342, 345-347, 357-359, and 372-377 are intermediates useful in making the final products. EXAMPLE 1 To 4-Chloroacetophenone 18.3 g (118 mmol) in an Erlenmeyer flask in absolute ethanol was added 4-isopropylbenzaldehyde 25.0 mL (165 mmol). This solution was cooled to 10°C and 10% sodium hydroxide in water, 7.8 mL, was added slowly. The solution was swirled continuously for 10 minutes, during which time an oil separated. Scratching the side of the flask with a glass rod caused crystallization. After 2 hours of intermittent mixing of the solid, it was collected by filtration and washed with 80% ethanol (50 mL) . The - 56 - solid was air dried giving 33.5 g (99%) of a light yellow solid which was identified by 1 H NMR, IR, MS. EXAMPLE 2 To the chalcone, 1, 33.5 g (188 mmol) in absolute ethanol (425 mL) at 55°C was added acetic acid 14 mL (236 mmol) followed by slow addition of potassium cyanide 20 g (308 mmol) in water (60 mL) . After 6 hours, thin layer analysis indicated that no starting chalcone remained; water (50 mL) was then added and the solution was cooled to 0°C. After 2 hours, a solid had precipitated and it was collected by filtration, washed with 75% ethanol (2X 50 mL) , and the solid was first air dried then dried at 0.5 mm Hg giving the nitrile as a colorless solid 29.0 g (79%); identified by 1 H NMR, IR, MS. EXAMPLE 3 To the nitrile, 2., 29 g (93 mmol) powdered in a mortar and pestle was added methanol (150 mL) . This - 57- mixture was saturated with hydrogen chloride gas and heated to 45°C until no starting nitrile remained upon thin layer analysis, water (30 mL) was then added, and the reaction was cooled in an ice bath. The solid that formed was removed by filtration and washed with 75% methanol (50 mL) followed by drying at 0.5 mm Hg. The ester, a colorless solid 20.5 g (64%) , was identified by ^ NMR, IR, MS. EXAMPLE 4 2 (5H) -Furanone. 5- (4-chlorophenyl) -5-hydrox - 3- 14- (l-methylethyl)phenyl1 -4- (phenylmethyl) - . (+) - To sodium metal 70 mg, (3.05 mmol) in methanol, (5 mL) was added benzaldehyde 0.325 mL (3.20 mmol) then the ester, 3., 1.0 g (2.90 mmol) . The resulting mixture was heated to reflux until the ester was consumed as determined by thin layer analysis. Acetic acid was added and the reflux was continued for 16 hours. The solvent was evaporated; flash chromatography of the residue 4:1 hexane/ethyl acetate provided the product 4. as a foam 816 mg (67%) that was identified by -"-H NMR, IR, [M + H] + - 419 Da. - 58 - EXAMPLE 5 The alcohol 3_9_ (1.0 g 2.37 mmol) in thionylchloride was heated at 55°C for 16 hours. The excess thionyl chloride was removed under reduced pressure to give an oil. This oil was taken up in a small volume of diethyi ether and hexane was added resulting in precipitation of the product as a tan solid. The solvent was decanted and the product was dried under a stream of nitrogen to give about 1 g (95%) of product that was utilized in crude form. EXAMPLE 6 (+) -3- (1.3-benzodioxol-5-yl) -5- (4-chlorophenyl) - 4- (phenylmethyl) -5- (2-propenyloxy) -2 (5H) -furanone The chloride (750 mg) , formed in a manner similar to Example 5, was heated at reflux with allyl alcohol - 59 - (5 mL) for 2 hours, excess alcohol was removed under reduced pressure, and the residue was chromatographed on SI0 2 4:1 hex/ethyl acetate giving a colorless oil 783 mg (95%) that was identified by ^-H NMR. EXAMPLE 7 Acetaldehyde. TT4- (1.3-benzodioxol-5-yl) - 2- (4-chlorophenyl) -2.5-dihydro-5-oxo-3- (phenylmethyl) - 2-furanylloxol - . (±) - The vinyl ether 6.516 mg (1.11 mmol) in dioxane/water 4:1 (5 mL) was treated with osmium tetroxide 2% (0.022 mmol) and sodium metaperiodate 502 mg (2.31 mmol) . After 6 hours, thin layer analysis indicated no starting ether remained. Ethyl acetate was added, the mixture was washed with water and then brine, followed by drying over magnesium sulfate. The solvent was evaporated tinder reduced pressure to give an oil that was chromatographed on silica gel 10% ethyl acetate/dichloromethane to give a colorless oil 324 mg (63%) that was identified by ^-H NMR, IR, [M + H] + = 463 Da. - 60 - EXAMPLE 8 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- (2.3-dihydroxypropoxy) - 4- (phenylmethyl)- . (+) - To the vinyl ether 6.259 mg (0.56 mmol) in dioxane/water 8:1 (9 L) was added osmium tetroxide 5% (0.028 mmol) and N-methylmorpholine-N-oxide (132 mg) (1.12 mmol) . After 4 hours, thin layer analysis indicated no starting ether remained; ethyl acetate was added, and the solution was washed with 10% H 2 S0 4 , brine, and then dried over magnesium sulfate to give an oil. Chromatography on silica gel 30% ethyl acetate/dichloromethane provided a colorless foam 176 mg (63%) that was identified by X H NMR, IR, [M + H] + = 494 Da. -61- EXAMPLE 9 Acetic acid, r T4- (1.3-benzodioxol-5-yl) -2- (4-chlorophenyl) -2.5-dihydro-3- (phenylmethyl) -5-oxo- 2-furanylloxyl - . (±) - The aldehyde 2220 mg (0.47 mmol) in acetone at 0°C was treated with Jones Reagent until a brown color persisted for 10 minutes, excess oxidant was removed by the addition of methanol. Ethyl acetate was then added, the solution was washed with water, brine, and then dried over magnesium sulfate to give a yellow oil 114 mg (51%) that was identified by ^-H NMR, IR, [M + H] + = 478 Da. -62- EXAMPLE 10 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- T (3-hydroxyphenyl)methoxy1 - 4- (phenylmethyl) - . (+) - To the chloride 500 mg (l.l mmol), formed as in Example 5, in dichloroethane (5 mL) was added 3-hydroxybenzyl alcohol and the solution was heated to reflux. After 16 hours, the solution was cooled and evaporated under reduced pressure. The residue was chromatographed on silica gel 7:3 hexane:ethyl acetate to give a colorless foam 471 mg (81%) that was identified by X H NMR, IR, [M + H] + = 526 Da. -63- EXAMPLE 11 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- (phenylamino) -4- (phenylmethyl) - . To the chloride 350 mg (0.79 mmol), prepared as in Example 5, in toluene (7 mL) was added aniline (145 μL, 1.6 mmol) . The solution was heated at 90°C for 16 hours cooled, and the solvent was evaporated under reduced pressure. Chromatography of the residue on silica gel 70:30 hexane/ether provided a foam 310 mg (79%) that was identified by x π NMR, IR, [M + H] + = 496 Da. -64- EXAMPLE 12 2(5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- (phenylmethyl) - 5- T (phenylmethyl)amino1 - . (+) - To alcohol 39_ 420 mg (1.0 mmol) in toluene (10 mL) was added benzylamine (0.5 mL) . The solution was heated to reflux for 24 hours, cooled, and the solvent was evaporated to give an oil. The residue was chromatographed on silica gel 3:1 hexane/ether, providing a colorless solid 123 mg (24%) that was identified by ^-H NMR, IR, [M + H] + = 510 Da. EXAMPLE 13 Following the procedure of Example 1 instead employing 4-methylacetophenone (14.76 g) and piperonal (23.1 g) , provided a solid 26.1 g (89%) that was identified by 1 H NMR, IR, MS, and microanalysis. -65- EXAMPLE 14 Following the procedure described in Example 2 instead employing 13. (25.5 g) , provided the nitrile as a dark solid 17.6 g (63%) that was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 15 Following the procedure described in Example 3 instead employing nitrile 14 (17.4 g) , provided the methyl ester as a solid 18.7 g (96%) that was identified by -"-H NMR, IR, MS, and microanalysis. - 66 - EXAMPLE 16 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydroxy- 5- (4-methylphenyl) -4- (phenylmethyl) - Following the procedure described in Example 4 instead employing the methyl ester 5 (1.30 g) , Na (97 mg) and benzaldehyde (467 mg) as the aldehyde, provide the lactone as a solid 0.85 g (53%) that was identified by ^-H NMR, IR, [M + H] + = 400 Da., and microanalysis. EXAMPLE 17 Following the procedure of Example 1 instead employing 4-methoxyacetophenone (16.5 g) and piperonal (23.12 g) , provided a solid 31.1 g (99%) that was identified by -"-H NMR, IR, MS, and microanalysis. -67- EXAMPLE 18 Following the procedure described in Example 2 instead employing 12 (31 g) , provided the nitrile as a dark solid 31.9 g (94%) that was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 19 Following the procedure described in Example 3 instead employing nitrile 18. (27.6 g) , provided the methyl ester as a " solid 28.1 g (92%) that was identified by 1 H NMR, IR, MS, and microanalysis. - 68 - EXAMPLE 20 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydrox - 5- (4-methoxyphenyl) -4- (phenylmethyl) - Following the procedure described in Example 4 instead employing the methyl ester .19 (1.36 g) , Na (97 mg) , and benzaldehyde (467 mg) as the aldehyde, provide the lactone as a foam 0.850 g (51%) that was identified by X H NMR, IR, [M + H] + = 416 Da., and microanalysis. EXAMPLE 21 Following the procedure of Example 1 instead employing acetophenone (13.2 g) and piperonal (23.12 g) , provided a light yellow solid 27.2 g (98%) that was identified 1 H NMR, IR, MS, and microanalysis. -69- EXAMPLE 22 Following the procedure described in Example 2 instead employing 21 (26.1 g) , provided the nitrile as a colorless solid 26.9 g (94%) that was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 23 Following the procedure described in Example 3 instead employing nitrile 22. (24.09 g) , provided the methyl ester as a tan solid 19.9 g (74%) that was identified by 1 H NMR, IR, MS, and microanalysis. -70- EXAMPLΞ 24 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydroxy- 5-phenyl-4- (phenylmethyl) - Following the procedure described in Example 4 instead employing the methyl ester 23. (1.25 g) , Na (97 mg) , and benzaldehyde (467 mg) as the aldehyde, provide the lactone as a foam 1.516 g (98%) that was identified by X H NMR, IR, [M + H] + = 386 Da., and microanalysis. EXAMPLE 25 2(5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydroxy- 5-phenyl-4- (2-thienylmethyl)- Following the procedure described in Example 4 instead employing the methyl ester 23. (1.25 g) , Na (97 mg) , and 2-thiophenecarboxaldehyde (493 mg) as the aldehyde, provide the lactone as a foam 1.15 g - 71- (73%) that was identified X H NMR, IR, [M + H] + = 392 Da., and microanalysis. EXAMPLE 26 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydroxy- 5-phenyl-4- (3-thienylmethyl) - Following the procedure described in Example 4 instead employing the methyl ester 23. (1.25 g) , Na (97 mg) , and 3-thiophene carboxaldehyde (493 mg) as the aldehyde, provide the lactone as a foam 0.800 g (51%) that was identified by ^-H NMR, IR, [M + H] + = 392 Da., and microanalysis. EXAMPLE 27 Following the procedure of Example l instead employing 4-chloroacetophenone (10.4 g) and 1,4-benzodioxan-6-carboxaldehyde (15.49 g) , provided a colorless solid 18.9 g (82%) that was identified by 1 H NMR, IR, MS, and microanalysis. -72- EXAMPLE 28 Following the procedure described in Example 2 instead employing 22 (12.25 g) , provided the nitrile as a colorless solid 11.9 g (89%) that was identified by X H NMR, IR, MS. EXAMPLE 29 Following the procedure described in Example 3 instead employing nitrile 28. (10 g) , provided the methyl ester as a solid 10.1 g (92%) that was identified by ^-H NMR, IR, MS. -73- EXAMPLE 30 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- (2.3-dihydro- 1.4-benzodioxin-6-yl) -5-hydroxy-4- (phenylmethyl) - Following the procedure described in Example 4 instead employing the methyl ester 29. (1.44 g) , Na (97 mg) , and benzaldehyde (467 mg) as the aldehyde, provide the lactone as a foam 0.495 g (28%) that was identified by ^-H NMR, IR, [M + H] + = 434 Da., and microanalysis. - 74 - EXAMPLE 31 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- \ (4-chlorophenyl)methyl! - 5-hydroxy- Following the procedure described in Example 4 only employing the methyl ester 32 (1.39 g) , Na (97 mg) , and p-chlorobenzaldehyde (0.619 g) as the aldehyde, provide the lactone as a tan solid 0.865 g (48%) that was identified by ^-H NMR, IR, [M + H] + = 454 Da. - 75 - EXAMPLE 32 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- 1 (4-methoxyphenyl) - methyl! - Following the procedure described in Example 4 only employing the methyl ester 32 (1.39 g) , Na (97 mg) , and p-anisaldehyde (0.60 g) as the aldehyde, provide the lactone as a tan solid 0.410 g (23%) that was identified by ^-H NMR, IR, [M + H] + = 450 Da. -76- EXAMPLE 33 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- T(4-methylphenyl) - methyl! - Following the procedure described in Example 4 only employing the methyl ester 31_ (1.39 g) , Na (97 mg) , and p-tolylaldehyde (528 mg) as the aldehyde, provide the lactone as a foam 0.50 g (29%) that was identified by X H NMR, IR, [M + H] + = 434 Da. - 77- EXAMPLE 34 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- \ (3-methylphenyl) - methyll - Following the procedure described in Example 4 only employing the methyl ester 2 (1.39 g) , Na (97 mg) , and m-tolylaldehyde (529 mg) as the aldehyde, provide the lactone as a foam 1.19 g (68%) that was identified by ^-H NMR, IR, [M + H] + = 434 Da. EXAMPLE 35 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (2-thienylmethyl) - Following the procedure described in Example 4 only employing the methyl ester 32 (1.39 g) , - 78 - Na (97 mg) , and 2-thiophenecarboxaldehyde (493 mg) as the aldehyde, provide the lactone as a foam 0.730 g (43%) that was identified by X H NMR, IR, [M + H] + = 426 Da. EXAMPLE 36 Following the procedure of Example 1 instead employing piperonal, provided a colorless solid 35.25 g (104%) that was identified by 1 H NMR, IR, MS, and found to contain traces of ethanol. EXAMPLE 37 Following the procedure described in Example 2 instead employing 3_6, provided the nitrile as a colorless solid 30 g (81%) that was identified by X H NMR. -79- EXAMPLE 38 Following the procedure described in Example 3 only employing 12, provided the nitrile as a colorless solid 12 g (36%) that was identified by ^-H NMR. EXAMPLE 39 2(5H) -Furanone. 3- (1.3-benzodioxol-5-yl)- 5- (4-chlorophenyl) -5-hydroxy-4- (phenylmethyl) - Following the procedure described in Example 4 only employing the methyl ester 18., and benzaldehyde as the aldehyde, provide the lactone as a foam 4.29 g (59%) that was identified by ^-H NMR, IR, MS. - 80 - EXAMPLE 40 2 (5H) -Furanone. 5- (4-chlorophenyl) -5-hydroxy- 3- T4- (1-methylethyl)phenyl1 -4- (1-naphthalenylmethyl) - . (*)- Following the procedure described in Example 4 only employing the methyl ester 1, and 1-naphthaldehyde as the aldehyde, provide the lactone as a foam 816 mg (60%) that was identified by E NMR, IR, [M + H] + = 468 Da. -81- EXAMPLE 41 2 (5H) -Furanone. 5- (4-chlorophenyl) -5-hydroxy- 3- T4- (l-methylethyl)phenyll -4- (2-naphthalenylmethyl) - . Following the procedure described in Example 4 only employing the methyl ester 3., and 2-naphthaldehyde as the aldehyde, provide the lactone as a foam 784 mg (58%) that was identified by X H NMR, IR, [M + H] + = 468 Da. -82- EXAMPLE 42 2(5H) -Furanone. 4- (1.3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -5-hydroxy-3- T4- (1-methylethyl) - phenyl! - . (+) - Following the procedure described in Example 4 only employing the methyl ester 1, and piperonal as the aldehyde, provide the lactone as a solid 687 mg (51%) that was identified by X H NMR, IR, [M + H] + = 462 Da. -83- EXAMPLE 43 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -5-hydroxy-4- (2-naphthalenylmethy1) - . (+) - Following the procedure described in Example 4 only employing the methyl ester 18., and 2-naphthaldehyde as the aldehyde, provide the lactone as a solid 861 mg (63%) that was identified by -"-H NMR, IR, [M + H] + = 462 Da. - 84 - EXAMPLE 44 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -5-hydroxy-4- (1-naphthalenylmethyl) - . (+) - Following the procedure described in Example 4 only employing the methyl ester 18, and 1-naphthaldehyde as the aldehyde, provide the lactone as a foam 1.02 g (75%) that was identified by X H NMR, IR, [M + H] + = 470 Da. -85- EXAMPLE 45 2(5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -5-hydroxy-4- T T4- (1-methylethyl) - phenvl!methyl! - . (+) - Following the procedure described in Example 4 only employing the methyl ester H, and 4-isopropylbenzaldehyde as the aldehyde, provide the lactone as a foam 743 mg (56%) that was identified by ^ ■ H NMR, IR, [M + H] + - 463 Da. EXAMPLE 46 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -4- (1.3-benzo¬ dioxol-5-ylmethyl) -5- (4-chlorophenyl) -5-hydroxy- . (+) - Following the procedure described in Example 4 only employing the methyl ester 18 and, piperonal as - 86 - the aldehyde, provide the lactone as a foam 815 mg (61%) that was identified by ^-H NMR, IR, MS. EXAMPLE 47 2(5H)-Furanone. 3- (1.3-benzodioxol-5-yl)- 5- (4-chlorophenyl) -5-hydroxy-4- T (3-methoxy¬ phenyl)methyl] - Following the procedure described in Example 4 only employing the methyl ester 12 (1.39 g) , Na (97 mg) , and m-anisaldehyde (0.60 g) as the aldehyde, provide the lactone as a light yellow solid 1.21 g (67%) that was identified by 1 H NMR, IR, [M + H] + = 450 Da. - 87- EXAMPLE 48 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -5-hydroxy-4- (3-thienylmethyl) - Following the procedure described in Example 4 only employing the methyl ester 17 (1.39 g) , Na (97 mg) , and 3-thiophenylaldehyde (493 mg) as the aldehyde, provide the lactone as a pale pink solid 0.690 g (40%) that was identified by X H NMR, IR, [M + H] + = 426 Da. EXAMPLE 49 Following the procedure of Example 1 only employing 4- (dimethylamino)benzaldehyde, provided a yellow solid 7.60 g (83%) that was identified by X H NMR, IR, MS. -88- EXAMPLE 50 Following the procedure described in Example 2 only employing 4 , provided the nitrile as a light brown solid 7.10 g (87%) that was identified by 1 H NMR, IR, MS. EXAMPLE 51 Following the procedure described in Example 3 only employing nitrile .5_0_, provided the methyl ester as a yellow solid 5.67 g (72%) that was identified by ^ NMR, IR, MS. -89- EXAMPLE 52 2 (5H) -Furanone. 5- (4-chlorophenyl) -3 T4- (dimethylamino) - phenyl] -5-hydroxy-4- (phenylmethyl) - . (+) - Following the procedure described in Example 4 only employing the methyl ester 5_l, and benzaldehyde as the aldehyde, provide the lactone as a pale yellow solid 0.300 g (26%) after purification by chromatography on silica gel using 1:9, ethyl acetate:hexane followed by crystallization from diethyi ether, and was identified by 1 H NMR, IR, [M + H] + = 420 Da. - 90 - EXAMPLE 53 2(5H) -Furanone. 5- (4-chlorophenyl) -5- (3.4-dichloro- phenyl)methyl! -3- \ (4-dimethylamino)phenyl! -5-hydroxy. (+)- Following the procedure described in Example 4 only employing the methyl ester .51, and 3,4-dichloro- benzaldehyde as the aldehyde, provide the lactone as a yellow solid 0.150 g (30%) after purification by chromatography on silica gel using 3:7, ethyl acetate:hexane followed by crystallization from diethyi ether and was identified by X H NMR, IR, [M + H] + - 488 Da. - 91- EXAMPLE 54 2(5H) -Furanone. 4- (1.3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -3- T4- (dimethlamino)phenyl! - 5-hydroxy- . (+) - Following the procedure described in Example 4 only employing the methyl ester 5_1, and piperonal as the aldehyde, provide the lactone as a yellow solid 0.18 g (43%) after purification by chromatography on silica gel using 1:4, ethyl acetate:hexane followed by crystallization from diethyi ether and was identified by X H NMR, IR, [M + H] + = 464 Da. - 92 - EXAMPLE 55 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- T4- (dimethla ino) - phenyl! -4- T [4- (dimethylamino)phenyl!methyl! -5-hydroxy- . Following the procedure described in Example 4 only employing the methyl ester j51, and p-dimethyl- aminobenzaldehyde as the aldehyde, provide the lactone as a yellow solid 0.40 g (59%) after purification by chromatography on silica gel using 1:4, ethyl acetate:hexane followed by crystallization from diethyi ether and was identified by 1 H NMR, IR, [M + H] + = 463 Da. -93- EXAMPLE 56 2 (5H) -Furanone. 5- (4-chlorophenyl) -4- (3.4-dimethox - phenyl) ethyl] -3- T4- (dimethylamino)phenyl! -5-hydroxy- . l±l. Following the procedure described in Example 4 only employing the methyl ester E51, and 3, -dimethoxy- benzaldehyde as the aldehyde, provide the lactone as a yellow foam 0.300 g (43%) after purification by chromatography on silic gel using 1:9, ethyl acetate:hexane followed by crystallization from diethyi ether, and was identified by 1 H NMR, IR, [M + H] + = 480 Da. - 94 - EXAMPLE 57 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- T (4- (dimethyl- amino)phenyl! -5-hydroxy-4- \T4- (1-methylethyl) - phenyl!methyl! - . (+) - Following the procedure described in Example 4 only employing the methyl ester J51, and 4-isopropyl- benzaldehyde as the aldehyde, provide the lactone as a yellow solid 0.150 g (27%) after purification on silica gel using 3:7, ethyl acetate:hexane followed by crystallization from diethyi ether and was identified by X Ω. NMR, IR, [M + H] + = 462 Da. EXAMPLE 58 Following the procedure of Example 1 only employing 3,4-dichlorobenzaldehyde, provided a colorless sol-id 35.9 g (80%) that was identified by ^ ■ H NMR, IR, MS. -95- EXAMPLE 59 Following the procedure described in Example 2 only employing 58., provided the nitrile as a colorless solid 16.2 g (42%) that was identified by X H NMR, IR, MS. EXAMPLE 60 Following the procedure described in Example 3 only employing nitrile 5_9_, provided the methyl ester after chromatography on silica gel 4:1 CH 2 C1 2 :hexane as a light brown oil 8.0 g (44%) that was identified by ^ ■ H NMR, IR, MS. -96 - EXAMPLE 61 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- (3.4-dichloro- phenyl) -5-hydrox -4- (phenylmethyl) - . (+) - Following the procedure in Example 4 only employing the methyl ester 6J3, and benzaldehyde as the aldehyde, provide the lactone as solid 948 mg (78%) that was identified by X H NMR, IR, [M + H] + = 445 Da. EXAMPLE 62 Following the procedure of Example 1 only employing 3,4-dimethoxybenzaldehyde, provided a colorless solid 31 g (86%) that was identified by X H NMR, IR, MS. -97- EXAMPLE 63 Following the procedure described in Example 2 only employing 62, provided the nitrile as a colorless solid 32.0 g (95%) that was identified by X H NMR, IR, MS. EXAMPLE 64 Following the procedure described in Example 3 only employing nitrile 61, provided the methyl ester as a light green solid 18.8 g (53%) that was identified by ^ • H NMR, IR, MS. - 98 - EXAMPLE 65 2 (5H) -Furanone. - (1.3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -3- (3.4-dimethoxyphenyl) -5-hydrox . (+)- Following the procedure described in Example 4 only employing the methyl ester § ., and piperonal as the aldehyde, provide the lactone as a foam 663 mg (46%) that crystalizes from diethyi ether and was identified by ^ NMR, IR; [M + H] + = 480 Da. -99- EXAMPLE 66 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro¬ phenyl) -5-hydroxy-4- T (1-methyl-lH-indol-3-yl)methyl] . Following the procedure described in Example 4 only employing the methyl ester 12, and 1-methylindole- 3-carboxaldehyde as the aldehyde, provide the lactone as a foam 276 mg (20%) that was identified by X H NMR, IR, [M + H] + = 474 Da. - 100 - EXAMPLE 67 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- (3.4-dimethoxy¬ phenyl) -5-hydroxy-4- (phenylmethyl) - . (*) - Following the procedure described in Example 4 only employing the methyl ester j>4., and benzaldehyde as the aldehyde, provide the lactone as a foam 692 mg (53%) that crystalizes from diethyi ether and was identified by X H NMR, IR, [M + H] + = 436 Da. EXAMPLE 68 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- (3.4-dimethoxy¬ phenyl) -4- T (3.4-dimethoxyphenyl)methyl1 -5-hydroxy- . (t)- Following the procedure described in Example 4 only employing the methyl ester .64., and 3,4-dimethoxy- - 101- benzaldehyde as the aldehyde, provide the lactone as a foam 810 mg (54%) that was identified by X H NMR, IR, [M + H] + = 496 Da. EXAMPLE 69 2(5H) -Furanone. 4- (1.3-benzodioxol-5-ylmethyl) - 5- (4-chlorophenyl) -3- (3.4-dichlorophenyl) -5-hydroxy- . (tj- Following the procedure described in Example 4 only employing the methyl ester .60., and piperonal as the aldehyde, provide the lactone as a foam l.ll g (85%) that crystalizes from diethyi ether and was identified by X H NMR, IR, [M + H] + = 488 Da. - 102 - EXAMPLE 70 2(5H) -Furanone. 5- (4-chlorophenyl) -3- (3.4-dimethoxy- phenyl) -5-hydroxy-4- T T4- (1-methylethyl)phenyl!methyl! - . Following the procedure described in Example 4 only employing the methyl ester .64 . , and 4-isopropyl- benzaldehyde as the aldehyde, provide the lactone as a foam 635 mg (44%) that crystalizes from diethyi ether and was identified by X H NMR, IR, [M + H] + = 478 Da. -103- EXAMPLE 71 2 (5H) -Furanone. 5- (4-chlorophenyl) -3- (3.4-dimethoxy¬ phenyl) -4- T T4- (dimethylamino)phenyl!methyl! -5-hydroxy- . Following the procedure described in Example 4 only employing the methyl ester 64., and 4- (dimethyl¬ amino)benzaldehyde as the aldehyde, provide the lactone as a foam 511 mg (34%) that crystalizes from diethyi ether and was identified by X H NMR, IR, [M + H] + = 480 Da. - 104 - EXAMPLE 72 2(5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -4- (phenylmethyl) -5-propoxy- . (+) - To a solution of 19. (50 mg, 0.12 mmol) in propanol (15 mL) was added HCl(g) until the solution was saturated. After 18 hours toluene was added and the solvent was evaporated to give an orange oil. Chromatography on silica gel (4:1 hexane:ethyl acetate) gave 34 mg (62%) as a colorless oil that was identified by X H NMR and [M + H] + = 463 Da. - 105 - EXAMPLE 73 2 (5H) -Furanone. 5- (4-chlorophenyl) -4- \ (3,4-dichloro- phenyl)me hyl! -3- (3.4-dimethoxyphenyl) -5-hvdroxy- . (+) Following the procedure described in Example 4 only employing the methyl ester from .64, and 3,4-dichlorobenzaldehyde as the aldehyde, provide the lactone as a solid 0.517 g (34%) after chromatography on silica gel (6% ethyl acetate in dichloromethane) followed by crystallization from diethyi ether, that was identified by X H NMR, IR, [M + H] + - 507 Da. -106- EXAMPLE 74 2(5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -4- T(3-chlorophenyl)methyl1 -5-hydroxy Following the procedure described in Example 4 only employing the methyl ester 12 (1.387 g) , Na (97 mg) , and m-chlorobenzaldehyde (0.619 g) as the aldehyde, provide the lactone as a light yellow solid 1.16 g (64%) that was identified by X H NMR, IR, [M + H] + = 439 Da. EXAMPLE 75 3-Benzon.3!dioxol-5-yl-4- (3-chlorobenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (2 mL) was added sodium methoxide (37 mg, 0.685 mmol) and stirred to dissolve. To this was added the ester, 19., (0.2 g, 0.585 mmol) then 3-chlorobenzaldehyde (95 mg, 0.685 mmol) . The mixture was heated to reflux for 4 hours. The solution was -107- then treated with acetic acid (2 mL) and refluxed an additional 16 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (100 g silica gel, 4:1 hexane:ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 179 mg (65%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 451 Da., and microanalysis. EXAMPLE 76 3-Benzori.3!dioxol-5-yl-5-hvdroxy-5- (4-methoxyphenyl) - 4- (4-methylbenzyl) -5H-furan-2-one To a solution of sodium methoxide (37 mg, 0.685 mmol) in methanol (2 mL) was added the ester 19. (0.2 g, 585 mmol) then 4-tolualdehyde (0.07 mL, 0.685 mmol) . The resulting mixture was heated to reflux for 4 hours. Acetic acid (0.5 mL) was added and the reflux continued for 16 hours,. The solvent was evaporated. Dissolved residue in ethyl acetate (100 mL) . Washed the organic phase with aqueous hydrochloric acid (IN, 80 mL) , then aqueous sodium chloride (saturated, 80 mL) . Dried the organic phase over magnesium sulfate. The solvent was evaporated. - 108 - Flash chromatography of the residue, eluted with 4:1 hexane:ethyl acetate provided the product as a foam (120 mg, 48%) that was identified by X H NMR, [M + H] + = 431 Da., IR, and elemental analysis. EXAMPLE 77 3-Benzori.3!dioxol-5-yl-5-hydroxy-4- (4-methoxybenzyl) - 5- (4-methoxyphenyl) -5H-furan-2-one To a solution of sodium methoxide (122 mg, 2.26 mmol) in methanol (7 mL) was added the ester .19. (0.7 g, 2.05 mmol) then 4-methoxybenzaldehyde (0.3 mL, 2.26 mmol) . The resulting mixture was heated to reflux for 4 hours. Acetic acid (2 mL) was added and the reflux continued for 16 hours. The solvent was evaporated. Dissolved residue in ethyl acetate (300 mL) . Washed the organic phase with aqueous hydrochloric acid (IN, 100 mL) , then aqueous sodium chloride (saturated, 100 mL) . Dried the organic phase over magnesium sulfate. The solvent was evaporated. Flash chromatography of the residue, eluted with 4:1 hexane:ethyl acetate provided the product as a foam (255 mg, 28%) that was identified by X H NMR, [M + H] + = 447 Da., IR, and elemental analysis. -109- EXAMPLE 78 3-Benzori.3!dioxol-5-yl- (3.4-dichlorobenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To a solution of sodium methoxide (174 mg, 3.22 mmol) in methanol (10 mL) was added the ester 19. (1.0 g, 2.924 mmol) then 3,4-dichlorobenzaldehyde (563 mg, 3.22 mmol). The resulting mixture was heated to reflux for 4 hours. Acetic acid (2 mL) was added and the reflux continued for 16 hours. The solvent was evaporated. Dissolved residue in ethyl acetate (300 mL) . Washed the organic phase with aqueous hydrochloric acid (IN, 100 mL) , then aqueous sodium chloride (saturated, 100 mL) . Dried the organic phase over magnesium sulfate. The solvent was evaporated. Flash chromatography of the residue, eluted with 4:1 hexane:ethyl acetate provided the product as a foam (838 mg, 60%) that was identified by X H NMR, [M + H] + = 485 Da., IR, and elemental analysis. -110- EXAMPLE 79 3-Benzof1.3!dioxol-5-yl-4- (4-tert-butylbenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (7 mL) was added soditim methoxide (0.122 g, 2.26 mmol) and stirred to dissolve. To this was added 4-tertbutyl-benzaldehyde (0.365 g, 2.26 mmol) then the ester, 19., (0.7 g, 2.05 mmol). The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 16 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and IN HC1 (100 mL) . The organic layer was washed with brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (25 g silica gel, 25% ethyl acetate/ hexane) . The butenolide was isolated by evaporation of the appropriate fractions 0.2 g (20%) as a white foam. The butenolide was identified by 1 H NMR, IR, MS, [M + H] + = 474 Da. -111- EXAMPLE 80 N-{4- T4-Benzor1.3!dioxol-5-yl-2-hydroxy- 2- (4-methoxyphenyl) -5-oxo-2.5-dihydro-furan- 3-ylmethyl! -phenyl}-acetamide To methanol (15 mL) was added sodium metal (253 mg, 11 mmol) and stirred to dissolve. To this was added the ester, 19, (3.42 g, 10 mmol) then 4-acetamidobenzaldehyde (1.63 g, 10 mmol). The mixture was heated to reflux for 20 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (120 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (500 g silica gel, 1:1, ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 2.90 g (61%) as a yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 474 Da., and microanalysis. -112- EXAMPLE 81 3-Benzori.3!dioxol-5-yl-4- (4-chlorobenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (2 mL) was added sodixαm methoxide (0.037 g, 0.685 mmol) and stirred to dissolve. To this was added 4-chlorobenzaldehyde (0.095 g, 0.685 mmol) then the ester, 19_, (0.2 g, 0.585 mmol) . This mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 16 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and IN HC1 (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (25 g silica gel, 25% ethyl acetate/ hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 0.179 g (65%) as a light yellow foam. The butenolide was identified by ^-H NMR, IR, MS, [M + H] + = 451 Da., and microanalysis. -113- EXAMPLE 82 3-Benzon.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (3-trifluoromethylenzyl) -5H-furan-2-one To dimethoxyethane (7 mL) was added potassixim- tert-butoxide (0.252 g, 2.25 mmol) and stirred to dissolve. To this was added 3-trifluoromethyl- benzaldehyde (0.39 g, 2.24 mmol) then the ester, 19_, (0.7 g, 2.0 mmol). The mixture was heated to reflux for 4.5 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and IN HC1 (90 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 0.184 g (19%) as a yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 485 Da. - 114 - EXAMPLE 83 3-Benzori.3!dioxol-5-yl-4- (4-bromobenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (7 mL) was added sodix_ιm metal (0.122 g, 2.26 mmol) and stirred to dissolve. To this was added 4-bromobenzaldehyde (0.416 g, 2.2 mmol) then the ester, 19, (0.7 g, 2.0 mmol). The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 16 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and IN HC1 (100 mL) . The organic layer was washed with brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (50 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 0.28 g (28%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] ÷ = 496 Da. - 115 - EXAMPLE 84 3-Benzo \1.3!dioxol-5-yl-5-hvdroxy-4- (isopropoxy- benzyl) -5- (4-methoxyphenyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (0.22 g, 9.6 mmol) and stirred to dissolve. To this was added 4-isoproxybenzaldehyde (1.59 g, 9.6 mmol) then the ester, .19., (3 g, 8.77 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (6 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and an aqueous saturated sodium bicarbonate (150 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (150 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (120 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions 1.6 g (38%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. - 116 - EXAMPLE 85 3-Benzori.3!dioxol-5-yl-4- (4-dimethylaminobenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodixm metal (0.12 g, 5.2 mmol) and stirred to dissolve. To this was added 4-dimethylaminobenzaldehyde (0.48 g, 3.2 mmol) then the ester, 19_, (1 g, 2.9 mmol). The mixture was heated to reflux for 16 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and an aqueous saturated sodium bicarbonate (100 mL) . The organic layer was washed with brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (80 g silica gel, 22% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fraction to give 0.38 g (28%) as a yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 460 Da. - 117- EXAMPLE 86 3-Benzo[1.3ldioxol-5-yl-4- (4-benzyloxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (15 mL) was added sodium metal (0.22 g, 9.6 mmol) and stirred to dissolve. To this was added 4-benzyloxybenzaldehyde (2.05 g, 9.6 mmol) then the ester, 19., (3 g, 8.8 mmol) . The mixture was heated to reflux for 8 hours. The solution was then treated with acetic acid (6 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and water (50 mL) . The organic layer was washed with brine (50 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (100 g silica gel, 25% ethyl acetate\hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether to give 2.4 g (22%) as a light blue solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 523 Da., and microanalysis. - 118 - EXAMPLE 87 3-BenzoTl.3!dioxol-5-yl-4-benzoTl.31dioxol-5-ylmethyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To isopropanol (5 mL) was added sodixrai metal (0.078 g, 3.4 mmol) and stirred to dissolve. To this was added piperonal (0.483 g, 3.2 mmol) then the ester, 19. (1 g, 2.9 mmol) . The mixture was heated to reflux for 8 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and an aqueous saturated sodium bicarbonate (100 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (2 x 100 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (70 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 0.28 g (21%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 461 Da. - 119 - EXAMPLE 88 3-Benzon.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (4-trifluoromethylbenzyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (0.164 g, 7.1 mmol) and stirred to dissolve. To this was added 4-trifluoromethylbenzaldehyde (1.475 g, 6.6 mmol) then the ester, 19., (2 g, 5.8 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (4 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (500 mL) and an aqueous saturated sodium bicarbonate (200 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (2 x 200 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (100 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 2.25 g (80%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 485 Da., and microanalysis. 3-Benzon.3!dioxol-5-yl-5-hydroxy-4- (4-methoxy- 3-methylbenzyl) -5- (4-methoxyphenyl) -5H-furan-2-one To methanol (15 mL) was added sodium metal (0.37 g, 16 mmol) and stirred to dissolve. To this was added 3-methyl-p-anisaldehyde (2.46 g, 16.4 mmol) then the ester, 19_, (5 g, 14.6 mmol). The mixture was heated to reflux for 16 hours. The solution was then treated with acetic acid (6 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and an aqueous saturated sodium bicarbonate (200 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (2 x 200 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (150 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether- methylene chloride to give 3.2 g (47%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 444 Da. , and microanalysis. -121- EXAMPLE 90 3-Benzof1.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (3-methylbenzyl) -5H-furan-2-one To t-butanol (3 mL) was added potassixun-t-butoxide (0.36 g, 3.2 mmol) and stirred to dissolve. To this was added m-tolualdehyde (0.386 g, 3.2 mmol) then the ester, 19., (l g, 2.9 mmol). The mixture was heated to 63°C for 5 hours. The solution was then treated with acetic acid (2 mL) and heated at 63°C for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and brine (100 mL) . The organic layer was washed with brine (100 mL) . The organic layer was dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (35 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions 0.489 g (39%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 431 Da., and microanalysis. r - 122 - EXAMPLE 91 3-Benzori.3!dioxol-5-yl-4-ethyl-5-hydroxy-5- (4-methoxy- phenyl) -5H-furan-2-one To DMF (5 mL) and methanol (1 mL) was added sodium methoxide (0.157 g, 2.9 mmol) and stirred to dissolve. To this was added acetaldehyde (2.5 g, 62.5 mmol) then the ester, 19., (1 g, 2.9 mmol). The mixture was stirred at 0°C for 4 hours, then warmed to room temperature for 16 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and IN HCl (100 mL) , washed with brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (30 g silica gel, 22% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.1 g (10%) as a yellow foam. The butenolide was identified by ^-H NMR, IR, MS, [M + H] + = 355 Da. - 123 - EXAMPLE 92 3-Benzori.3!dioxol-5-yl-4- (3-chloro-4-methoxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol was added sodium metal (0.2 g, 8.7 mmol) and stirred to dissolve. To this was added 3-chloro-4-methoxybenzaldehyde (1.65 g, 8.8 mmol) then the ester, 1£, (3 g, 8.8 mmol) . The mixture was heated to reflux for 16 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and an aqueous saturated sodium bicarbonate (150 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (150 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 1.71 g (41%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 481 Da., and microanalysis. - 124 - EXAMPLE 93 3-BenzoT1.3!dioxol-5-yl-4- (4-butoxybenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (0.22 g, 9.6 mmol) and stirred to dissolve. To this was added 4-butoxybenzaldehyde (1.7 g, 9.6 mmol) then the ester, 19_, (3 g, 8.8 mmol). The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and an aqueous saturated sodium bicarbonate (200 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (200 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 2 g (46%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 489 Da., and microanalysis. -125- EXAMPLE 94 To 4-methoxyacetophenone (21.4 g, 142 mmol) in absolute ethanol (35 mL) in an erlenmeyer was added 4-chlorobenzaldehyde (20 g, 142 mmol) . The solution swirled while 10% sodium hydroxide (6 mL) added. The mixture swirled for 1 hour and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 35 g (90%) of a yellow solid which was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 95 Cl To the chalcone, 94., (35 g, 129 mmol) in 2-ethoxy- ethanol (200 mL) at 105°C was added acetic acid (8.1 mL) followed by slow addition of potassium cyanide (12.53 g, 193 mmol) in water (25 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was - 126 - cooled. Product crystallized. Filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (200 mL) , air dried, and then dried in vacuo to give the nitrile, 29.62 g (77%) . The nitrile was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 96 To the nitrile, f>5, (5 g, 16.7 mmol) was added methanol (180 mL) . The mixture was saturated with HCl (g) and stirred at room temperature until no nitrile remained by thin-layer chromatography. The solvent was removed at reduced pressure and the residue was partitioned between ethyl acetate (200 mL) and water (100 mL) . The organic phase was washed with brine (100 mL) and dried over MgS0 4 . The solvent was removed at reduced pressure and the residue was dissolved with hot methanol. This solution was treated with charcoal and filtered. The ester, £6., 4.2 g (76%) crystallized upon cooling the filtrate to room temperature. The ester was identified by 1 H NMR, IR, MS, and itiicroanalysis. - 127- EXAMPLE 97 3- (4-Chlorophenyl) -5-hydroxy-4- (4-methoxybenzyl) - 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (10 mL) was added sodixim metal (0.15 g, 6.6 mmol) and stirred to dissolve. To this was added p-anisaldehyde (0.9 g, 6.6 mmol) then the ester, £6., (2 g, 6 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and an aqueous saturated sodium bicarbonate (150 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (150 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 1.5 g (60%) as white crystals. The butenolide was identified by ^ NMR, IR, MS, [M + H] + = 437 Da., and microanalysis. -128- EXAMPLE 98 To 4-methoxyacetophenone (13 g, 86 mmol) in absolute ethanol (70 mL) in an erlenmeyer was added p-anisaldehyde (11.78 g, 86 mmol). The solution swirled while 10% sodium hydroxide (8 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid Was dried in vacuo giving 14.66 g (63%) of a solid which was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 99 To the chalcone, 9_8, (14.66 g, 54.7 mmol) in 2-ethoxyethanol (90 mL) at 55°C was added acetic acid (3.3 mL) followed by slow addition of potassium cyanide (5.34 g, 82 mmol) in water (15 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was - 129 - cooled, product crystallized. The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (200 mL) , air dried, and then dried in vacuo to give the nitrile 14.42 g (89%) The nitrile was identified by 1 H NMR, IR, MS, and microanalysis. EXAMPLE 100 To the nitrile, £9., (10.1 g, 34.2 mmol) was added methanol. (200 mL) . The mixture was saturated with HCl (g) and stirred at room temperature until no nitrile remained by thin-layer chromatography. The solvent was removed at reduced pressure and the residue was partitioned between ethyl acetate (200 mL) and water (100 mL) . The organic phase was washed with brine (100 mL) and dried over MgS0 4 . The solvent was removed at reduced pressure and the residue was dissolved with hot methanol. This solution was treated with charcoal and filtered. The ester, 100. 1.76 g (16%) crystallized upon cooling the filtrate to room temperature. The ester was identified by X H NMR, IR, MS, and microanalysis. -130- EXAMPLE 101 5-Hydroxy-4- (4-methoxybenzyl) -3.5-bis- (4-methoxy- phenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.12 g, 5.2 mmol) and stirred to dissolve. To this was added p-anisaldehyde (0.72 g, 5.3 mmol) then the ester, 100. (1.5 g, 4.6 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and an aqueous saturate sodium bicarbonate (200 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (200 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 0.63 g (32%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 433 Da., and microanalysis. -131- EXAMPLE 102 To 4-methoxyacetophenone (12.23 g, 80 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added tolualdehyde (9.6 g, 80 mmol) . The solution swirled while 10% sodium hydroxide (8 mL) added. The mixture swirled for 1 hour and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 19 g (92%) solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 103 To the chalcone, 102. (25.4 g, 100 mmol) in 2-ethoxyethanol (90 mL) at 105°C was added acetic acid (6.4 mL) followed by slow addition of potassium cyanide (9.83 g, 150 mmol) in water (20 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was cooled, product crystallized out. The mixture was then filtered to collect the solid. The solid was washed - 132 - repeatedly with 70% ethanol (200 mL) , air dried, and then dried in vacuo to give the nitrile 24 g (85%) . The nitrile was identified by -"-H NMR, IR, MS, and microanalysis. EXAMPLE 104 To the nitrile, 103. (10.7 g, 38.4 mmol) was added methanol (200 mL) . The mixture was saturated with HCl (g) and stirred at room temperature until no nitrile remained by thin-layer chromatography. The solvent was removed at reduced pressure and the residue was partitioned between ethyl acetate (200 mL) and water (100 mL) . The organic phase was washed with brine (100 mL) and dried over MgS0 4 . The solvent was removed at reduced pressure and the residue was dissolved with hot methanol. This solution was treated with charcoal and filtered. The ester, 104. 6.25 g (52%) crystallized upon cooling the filtrate to room temperature. The ester was identified by 1 H NMR, IR, MS, and microanalysis. -133- EXAMPLE 105 5-Hydroxy-4- (4-methoxybenzyl) -5- (4-methoxyphenyl) - 3-p-tolyl-5H-furan-2-one To methanol (8 mL) was added sodium metal (0.16 g, 7 mmol) and stirred to dissolve. To this was added p-anisaldehyde (0.96 g. 7 mmol) then the ester, 104. (2 g, 6.4 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid 4 mL and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and an aqueous saturated sodium bicarbonate (100 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (100 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/ hexane) . The butenolide was isolated by evaporation of the appropriate fraction and crystallized from isopropyl ether-methylene chloride to give 1 g (37.5%) as white crystals. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 417 Da., and microanalysis. - 134 - EXAMPLE 106 To 4-methoxyacetophenone (12 g, 80 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added benzaldehyde (8.13 g, 80 mmol). The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 15.34 g (80%) of a white solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 107 To the chalcone, 106. (15.34 g, 64 mmol) in 2-ethoxyethanol (90 mL) at 105°C was added acetic acid (4.1 mL) followed by slow addition of potassium cyanide (6.3 g, 96.6 mmol) in water (15 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was cooled, product crystallized. The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (200 mL) , air dried, and then dried in vacuo to give the nitrile 11.6 g (66%) . - 135 - The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 108 To the nitrile, 107. (10.5 g, 39.6 mmol) was added methanol (200 mL) . The mixture was saturated with HCl (g) and stirred at room temperature until no nitrile remained by thin-layer chromatography. The solvent was removed at reduced pressure and the residue was partitioned between ethyl acetate (200 mL) ' and water (200 mL) . The organic phase was washed with brine (100 mL) and dried over MgS0 4 . The solvent was removed at reduced pressure and the residue was dissolved with hot methanol. This solution was treated with charcoal and filtered. The ester, 108. 4.8 g (40%) crystallized upon cooling the filtrate to room temperature. The ester was identified by X H NMR, IR, MS, and microanalysis. 5-Hydroxy-4- (4-methoxybenzyl) -5- (4-methoxyphenyl) - 3-phenyl-5H-furan-2-one To methanol (8 mL) was added sodium metal (0.18 g, 8.2 mmol) and stirred to dissolve. To this was added p-anisaldehyde (0.96 g, 8.2 mmol) then the ester, 108. (1.9 g, 6.3 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (4 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (300 mL) and an aqueous saturated sodium bicarbonate (150 mL) . The organic layer was washed with aqueous ' saturated sodium bicarbonate (150 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 1.03 g (40%) as a yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 403 Da., and microanalysis. -137- EXAMPLE 110 To 2,4-dimethoxybenzaldehyde (12.17 g, 72 mmol) in absolute ethanol (30 mL) in an erlenmeyer was added 4-methoxyacetophenone (10.0 g, 66.6 mmol). The solution swirled while 10% sodium hydroxide (4.5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (70 mL) . The solid was dried in vacuo giving 17.1 g (86%) of a yellow solid which was identified by X H NMR, IR, and MS. EXAMPLE 111 To the chalcone, 110. (17.0 g, 57 mmol) in ethanol:chloroform 5:1 (240 mL) at 55°C was added acetic acid (6.5 mL) followed by slow addition of potassium cyanide (9.26 g, 143 mmol) in water (20 mL) . The solution was stirred at 55°C for 48 hours. The chloroform was evaporated and the solution was allowed to stand 14 hours during which time a solid was deposited. The solid was collected by filtration, then dissolved in ethyl acetate/dichloromethane and - 138 - decolorized with norite. Filtration and evaporation gave a tan solid 13.0 g (70%) . The nitrile was identified by X H NMR, IR, and MS. EXAMPLE 112 To the nitrile. 111. (2.0 g, 5.6 mmol) was added methanol (20 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and water was added. Extraction with ethyl acetate provided a green oil that was chromatographed on silica gel (2:1, hexane/ethyl acetate) to give the ester, 945 mg (47%) , as a colorless solid. EXAMPLE 113 4-Benzyl-3- (2.4-dimethoxyphenyl) -5-hydrox - 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodixim metal (67 mg, 2.9 mmol) and stirred to dissolve. To this was added - 139 - benzaldehyde (300 mg, 2.9 mmol) then the ester, 112. (950 mg, 2.65 mmol) . The mixture was heated to reflux for 10 hours. The solution was split, and half then treated with acetic acid (5 mL) and refluxed for an additional 30 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (200 g silica gel, 3% methanol/ dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 118 mg (10%) as a solid. The butenolide was identified by ■ " • H NMR, IR, MS, [M + H] + = 433 Da., and microanalysis. EXAMPLE 114 To 3,4-dichlorobenzaldehyde (18.3 g, 105 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added 4-methoxyacetophenone (15.0 g, 100 mmol) . The solution swirled while 10% sodium hydroxide (7 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (70 mL) . The solid was dried in vacuo giving 31.7 g (103%) of a light yellow solid which was identified by 1 H NMR, IR, and MS. -140- EXAMPLE 115 To the chalcone, 114. (31.7 g, 103 mmol) in ethanol:chloroform 5:1 (420 mL) at 55°C was added acetic acid (11.8 mL) followed by slow addition of potassium cyanide (16.8 g, 255 mmol) in water (50 mL) . The solution was stirred at 60°C for 6 hours. The solution was cooled and the chloroform removed on a rotovap, water (100 mL) was added, and the solution was cooled to 0°C. The resulting precipitate was collected by filtration, air dried, and then dried in vacuo to give the nitrile 33.6 g (98%) as a light brown solid. The nitrile was identified by λ K NMR, IR, and MS. EXAMPLE 116 To the nitrile, 115. (16.0 g, 47.9 mmol) was added methanol (300 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (60 mL) . The gummy precipitate was taken up in dichloromethane and washed with water and brine. After drying over magnesium sulfate, the solvent was evaporated to give a brown foam. -141- Chromatography Si0 2 (4:1, dichloromethane: exane) gave a solid, the ester 8.75 g (49%) which was identified by ^ ■ H NMR, IR, and MS. EXAMPLE 117 3- (3.4-Dichlorophenyl) -5-hydroxy-4- (4-methoxybenzyl) - 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (0.14 g, 6.1 mmol) and stirred to dissolve. To this was added p-anisaldehyde (0.84 g, 6.1 mmol) then the ester, 116. (2 g, 5.5 mmol) . The mixture was heated to reflux for 20 hours. The solution was then treated with acetic acid (4 mL) and refluxed for an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and an aqueous saturated sodium bicarbonate (100 mL) . The organic layer was washed with aqueous saturated sodium bicarbonate (100 mL) , then brine (100 mL) . The organic layer was then dried over MgS0 4 and evaporated to dryness. The crude material was purified by flash chromatography (40 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions and crystallized from isopropyl ether-methylene chloride to give 1.4 g (55%) as white crystals. The butenolide was ■ 142 ' identified by X H NMR, IR, MS, [M + H] + = 472 Da., and microanalysis. EXAMPLE 118 5- (4-Chlorophenyl) -3- (3.4-dichlorophenyl) -5-hydrox - 4- (4-isopropylbenzyl) -5H-furan-2-one To methanol (5 mL) was added sodixim metal (68 mg, 2.9 mmol) and stirred to dissolve. To this was added cuminaldehyde (0.45 mL, 2.9 mmol) then the ester, 60. (1.0 g, 2.7 mmol). The mixture was heated to reflux for 16 hours. The solution was then treated with acetic acid (7 mL) and refluxed for an additional 6 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (250 g silica gel, 2% ethyl acetate/ dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 840 mg (65%) as a colorless foam. The butenolide was identified by ^-H NMR, IR, MS, [M + H] + = 488 Da., and microanalysis. -143- EXAMPLE 119 5- (4-Chlorophenyl) -3- (3.4-dichlorophenyl) - 4- (4-dimethylaminobenzyl) -5-hydroxy-5H-furan-2-one To methanol (5 mL) was added sodium metal (68 g, 2.9 mmol) and stirred to dissolve. To this was. added 4- (dimethylamino)benzaldehyde (440 mg, 2.9 mmol) then the ester, 6O, (1.0 g, 2.7 mmol). The mixture was heated to reflux for 16 hours. The solution was then treated with acetic acid (7 mL) and refluxed an additional 6 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (250 g silica gel, 4% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 290 mg (22%) as a light yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 489 Da., and microanalysis. -144- EXAMPLE 120 4-Benzyl-3- (3.4-dichlorophenyl) -5-hydroxy-5- (4-methoxy- phenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (35 mg, 1.5 mmol) and stirred to dissolve. To this was added benzaldehyde (152 μL, 1.5 mmol) then the ester, 115. (500 mg, 1.36 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (7 mL) and refluxed an additional 16 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (250 g silica gel, 4% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 479 mg (80%) as a colorless foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 442 Da., and microanalysis. -145- EXAMPLE 121 3- (3.4-Dichlorophenyl) -5-hydroxy-4- (4-isopropyl- benzyl) -5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (35 mg, 1.5 mmol) and stirred to dissolve. To this was added cuminaldehyde (228 μL, 1.5 mmol) then the ester, 115. (500 mg, 1.36 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (7 mL) and refluxed an additional 16 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (250 g silica gel, 4% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 489 mg (74%) as a colorless foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 484 Da., and microanalysis. -146- EXAMPLE 122 To 3,5-dimethoxyacetophenone (15.0 g, 99.88 mmol) in absolute ethanol (70 mL) in an erlenmeyer was added 4-methoxybenzaldehyde (23.24 g, 139.83 mmol). The solution swirled while 10% sodium hydroxide (10 mL) added. The mixture swirled for 1 hour and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 200 mL) . The solid was dried in vacuo giving 28.5 g (95%) of a pale yellow solid which was identified by 1 H NMR. EXAMPLE 123 To the chalcone, 122. (10 g, 33.52 mmol) in 2-ethoxyethanol (50 mL) at 55°C was added acetic acid (3.80 mL) followed by slow addition of potassium cyanide (5.45 g, 83.80 mmol) in water (10 mL) . The solution was stirred at 105°C for 10 hours. The solution was cooled and evaporated to dryness. The cirude product was then purified by flash chromatography (500 g silica gel eluent, 20% ethyl acetate/hexane) . -147- Dried in vacuo to give the nitrile, 7.60 g (69%) as a dark green solid. The nitrile was identified by X H NMR. EXAMPLE 124 To the nitrile, 123. (3 g, 9.22 mmol) was added methanol (30 mL) . The mixture was saturated with HCl (g) and heated to 80°C until no nitrile remained, by thin-layer chromatography. The solution was cooled. The solution was evaporated to dryness, then purified on 300 g Si0 2 eluent 15% ethyl acetate/hexane. This gave the ester 1.10 g (33%) as a light brown semisolid which was identified by X H NMR, IR, MS, and microanalysis. -148- EXAMPLE 125 4-Benzyl-3- (3.5-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.021 g, 0.92 mmol) and stirred to dissolve. To this was added benzaldehyde (0.10 g, 0.92 mmol) then the ester, 124. (0.3 g, 0.84 mmol). The mixture was heated to reflux for 3 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/ hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.20 g (55%) as a light brown solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 433 Da., and microanalysis. - 149 - EXAMPLE 126 3- (3.5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - 4- (3-propoxybenzyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.03 g, 1.20 mmol) and stirred to dissolve. To this was added 3-O-propylbenzaldehyde (0.18 g, 1.10 mmol) then the ester, 124. (0.35 g, 0.98 mmol) . The mixture was heated to reflux for 10 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 5 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.26 g (54%) as an amorphous glass. The butenolide was identified by ^ NMR, IR, MS, [M + H] + = 491 Da., and HPLC = 97.97%. -150- EXAMPLE 127 4- (3-Chlorobenzy1) -3- (3.5-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.017 g, 0.75 mmol) and stirred to dissolve. To this was added 3-chlorobenzaldehyde (0.078 g, 0.55 mmol) then the ester, 124. (0.18 g, 0.5 mmol). The mixture was heated to reflux for 10 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 8 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.13 c (55%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 467 Da., and HPLC = 98.76%. -151- EXAMPLE 128 3- (3.5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - 4- (3-trifluoromethylbenzyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.014 g, 0.614 mmol) and Stirred to dissolve. To this was added 3-trifluoromethylbenzaldehyde (0.107 g, 0.614 mmol) then the ester, 124. (0.20 g, 0.56 mmol) . The mixture was heated to reflux for 10 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 8 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.15 g (53%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 501 Da., and HPLC = 99.5%. -152- EXAMPLE 129 3- (3.5-Dimethoxyphenyl) -4- (3-fluorobenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.023 g, 1.00 mmol) and stirred to dissolve. To this was added 3-fluorobenzaldehyde (0.114 g, 0.92 mmol) then the ester, 124. (0.30 g, 0.837 mmol). The mixture was heated to reflux for 10 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (170 g silica gel, eluent 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.24 g (63%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + - 451 Da., and microanalysis. -153- EXAMPLE 130 3- (3.5-Dimethoxyphenyl) -5-hydroxy-4- (3-methoxybenzyl) - 5- (4- ethoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.023 g, 1.0 mmol) and stirred to dissolve. To this was added 3-methoxybenzaldehyde (0.125 g, 0.92 mmol) then the ester, 124. (0.30 g, 0.834 mmol). The mixture was heated to reflux for 10 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.30 g (77%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 463 Da., and microanalysis. -154- EXAMPLE 131 3- (3.5-Dimethoxyphenyl) -5-hydroxy-4- (4-methoxybenzyl) - 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.023 g, 1.0 mmol) and stirred to dissolve. To this was added 4-methoxybenzaldehyde )0.125 g, 0.92 mmol) then the ester, 124. (0.3 g, 0.837 mmol). The mixture was heated to reflux for 72 hours. The solution was then treated with acetic acid and refluxed an additional 24 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.10 c (26%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 463 Da., and HPLC = 95%. -155- EXAMPLE 132 4- (3.5-Dichlorobenzyl) -3- (3.5-dimethoxyphenyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodixim metal (0.03 g, 1.0 mmol) and stirred to dissolve. To this was added 3,5-dichlorobenzaldehyde (0.161 g, 0.92 mmol) then the ester, 124. (0.3 g, 0.837 mmol). The mixture was heated to reflux for 3 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 3 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.24 < (57%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 501 Da., and microanalysis. -156- EXAMPLE 133 3- (3.5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - 4-pyridin-3-ylmethyl-5H-furan-2-one To methanol (5 mL) was added sodium metal (0.038 g, 1.68 mmol) and stirred to dissolve. To this was added 3-pyridylcarboxaldehyde (0.164 g, 1.53 mmol) then the ester, 124. (0.5 g, 1.40 mmol). The mixture was heated to reflux for 2 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 5 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 25% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.50 (82%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + - 434 Da., and HPLC = 98.74%. -157- EXAMPLE 134 3- T4- (3.5-Dimethoxyphenyl) -2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydrofuran-3-ylmethyl!benzaldehyde To methanol (5 mL) was added sodium metal (0.023 g, 1.00 mmol) and stirred to dissolve. To this was added 3-formylbenzaldehyde (0.225 g, 1.67 mmol) then the ester, 124. (0.30 g, 0.837 mmol) . The mixture was heated to reflux for 1 hour. The solution was then treated with acetic acid (5 mL) and refluxed an additional 8 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.28 g (72%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 461 Da., and microanalysis. -158- EXAMPLE 135 4- (3-Allyloxy-4-methoxybenzyl) -3- (3.5-dimethoxy¬ phenyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.023 g, 1.0 mmol) and stirred to dissolve. To this was added 3-alloxy-p-anisaldehyde (0.295 g, 1.53 mmol) then the ester, 124. (0.5 g, 1.40 mmol) . The mixture was heated to reflux for 12 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.30 g (41%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 519 Da., and microanalysis. - 159 - EXAMPLE 136 To p-methoxyacetophenone (2.74 g, 18.22 mmol) in THF (60 mL) in an erlenmeyer was added pentafluoro- benzaldehyde (5.0 g, 25.50 mmol). The solution swirled while 10% sodium hydroxide (20 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 ml) . The solid was dried in vacuo giving 2.61 g (31%) of a light brown solid which was identified by X H NMR. EXAMPLE 137 To the chalcone, 136. (2.61 g, 7.35 mmol) in 2-ethoxyethanol (30 mL) at 55°C was added acetic acid (5 mL) followed by slow addition of potassium cyanide (1.19 g, 18.37 mmol) in water (5 mL) . The solution was stirred at 105°C for 12 hours. The solution was cooled. The solution was evaporated. The crude product was purified on 170 g of Si0 2 10% ethyl - 160- acetate/hexane to give the nitrile 0.4 g (15%) as a solid. The nitrile was identified by X H NMR. EXAMPLE 138 To the nitrile, 137. (0.4 g, 1.12 mmol) was added methanol (1.0 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (5 mL) . The resultant gummy stuff oiled out, decanted the solvent, and the residue dried in vacuo. This gave the ester 0.37 g (85%) as a light brown solid which was identified by X H NMR. EXAMPLE 139 4-Benzyl-5-hvdroxy-5- (4-methoxyphenyl) - 3- (2.3.4.5.6-pentafluorophenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.026 g, 1.14 mmol) and stirred to dissolve. To this was added benzaldehyde (0.111 g, 1.05 mmol) then the - 161- ester, 138. (0.37 g, 0.953 mmol). The mixture was heated to reflux for 12 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.10 g (22%) as a purple color solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 463 Da., and microanalysis. EXAMPLE 140 To 4-methoxyacetophenone (7.0 g, 41.13 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added 3,4-difluorobenzaldehyde (8.18 g, 57.6 mmol). The solution swirled while 10% sodium hydroxide (4 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 10.50 g (93%) of a pale yellow solid which was identified by X H NMR. -162- EXAMPLE 141 To the chalcone, 140. (5.05 g, 18.23 mmol) in -ethoxyethanol (40 mL) at 55°C was added acetic acid (2.10 mL) followed by slow addition of potassium cyanide (3.0 g, 45.6 mmol) in water (5.0 mL) . The solution was stirred at 105°C for 12 hours. The solution was cooled and treated with water (5 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (2 x 100 mL) , air dried, and then dried in vacuo to give the nitrile 4.2 g (76%) as an off-white solid. The nitrile was identified by X H NMR. EXAMPLE 142 To the nitrile, 141. (1.57 g, 5.20 mmol) was added methanol (40 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (5 mL) . The resultant solid was filtered to collect, washed with 80% methanol (2 x 250 mL) , and dried in vacuo. This gave the ester 1.5 g (86%) as a solid which was identified by X H NMR. - 163 - EXAMPLE 143 4-Benzyl-3- (3.4-difluorophenyl) -5-hydroxy-5- (4-methoxy- phenyl) -5H-furan-2-one To methanol (5 mL) was added sodixim metal (0.024 g, 1.04 mmol) and stirred to dissolve. To this was added benzaldehyde (0.105 g, 0.987 mmol) then the ester, 142. (0.3 g, 0.90 mmol) . The mixture was heated to reflxix for 4 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/ hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.25 g (68%) as a light brown solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 409 Da., and microanalysis. -164- EXAMPLE 144 3- (3.4-Difluorophenyl) -5-hydroxy-4- (4-isopropyl- benzyl) -5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.024 g, 1.04 mmol) and stirred to dissolve. To this was added cuminaldehyde (0.146 g, 0.987 mmol) then the ester, 142. (0.3 g, 0.897 mmol). The mixture was heated to reflux for 8 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.20 g (49%) as an off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 451 Da., and microanalysis. -165- EXAMPLE 145 3- (3.4-Difluorophenyl) -4- (4-dimethylaminobenzyl) - 5-hydroxy-5- (4- ethoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodixαm metal (0.016 g, 0.72 mmol) and stirred to dissolve. To this was added 4-dimethylaminobenzaldehyde (0.10 g, 0.66 mmol) then the ester, 142. (0.2 g, 0.60 mmol). The mixture was heated to reflux for 12 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.06 g (22%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 452 Da., and HPLC = 90%. - 166 - EXAMPLE 146 To 4-methoxyacetophenone (3.064 g, 20.40 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added 3,5-dichlorobenzaldehyde (5.0 g, 28.57 mmol). The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 6.44 g (73%) of a pale yellow solid which was identified by X H NMR. EXAMPLE 147 To the chalcone, 146. (6.44 g, 20.96 mmol) in 2-ethoxyethanol (50 mL) at 55°C was added acetic acid (1.33 mL) followed by slow addition of potassium cyanide (2.044 g, 31.44 mmol) in water (5.0 mL) . The solution was stirred at 105°C for 12 hours. The solution was cooled and treated with water. The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (2 x 100 mL) , air dried, and then dried in vacuo to - 167 - give the nitrile 6.51 g (92%) as a dark green solid. The nitrile was identified by X H NMR. EXAMPLE 148 To the nitrile, 147. (2.2 g, 6.60 mmol) was added methanol (70 mL) . The mixture was saturated with HCl (g) and heated to 80°C until no nitrile remained, by thin-layer chromatography. The solution was cooled. The solution was evaporated to dryness. The crude product was purified on Si0 2 170 g (15% ethyl acetate/ hexane) . This gave the ester 0.35 g (15%) as a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 149 4-Benzyl-3- (3.5-dichloro-henyl) -5-hydroxy-5- (4-methoxy- phenyl) -5H-furan-2-one To methanol (5 mL) was added sodixim metal (0.015 g, 0.65 mmol) and stirred to dissolve. To this was added benzaldehyde (0.064 g, 0.60 mmol) then the -168- ester, 148. (0.2 g, 0.544 mmol). The mixture was heated to reflux for 3 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 10% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.12 g (50%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 441 Da., and microanalysis. EXAMPLE 150 To 4-methoxyacetophenone (15 g, 97.88 mmol) in absolute ethanol (70 mL) in an erlenmeyer was added aldehyde (19.10 g, 139.84 mmol). The solution swirled while 10% sodium hydroxide (10 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 100 mL) . The solid was dried in vacuo giving 24.70 g (92%) of a pale yellow solid which was identified by X H NMR. -169- EXAMPLE 151 To the chalcone, 150. (10.0 g, 37.27 mmol) in 2-ethoxyethanol (50 mL) at 55°C was added acetic acid (2.35 mL) followed by slow addition of potassium cyanide (3.64 g, 55.90 mmol) in water (1.0 mL) . The solution was stirred at 105°C for 12 hours. The solution was cooled. The solution was evaporated to dryness, purified on Si0 2 (400 g) (30% ethyl acetate/ hexane) to give the nitrile 9.48 g (86%) as a dark green oil. The nitrile was identified by X H NMR. EXAMPLE 152 To the nitrile, 151. (3 g, 10.16 mmol) was added methanol (20 mL) . The mixture was saturated with HCl (g) and heated to 80°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (10 mL) . The resultant solid was filtered to collect, washed with 80% methanol (2 x 20 mL) , and dried in vacuo. This gave the ester 3.10 g (92%) as a gray solid which was identified by X H NMR. -170- EXAMPLE 153 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) -3- (3-methoxy¬ phenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.042 g, 1.82 mmol) and stirred to dissolve. To this was added benzaldehyde (0.177 g, 1.70 mmol) then the ester, 152. (0.5 g, 1.52 mmol) . The mixture was heated to reflxix for 12 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, eluent 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.35 g as a dark orange semi-solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 403 Da., and microanalysis. -171- EXAMPLE 154 5-Hydroxy-5- (4-methoxyphenyl) -3- (3-methoxyphenyl) - 4- (3-propoxybenzyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.03 g, 1.28 mmol) and stirred to dissolve. To this was added benzaldehyde (0.193 g, 1.20 mmol) then the ester, 152. (0.35 g, 1.066 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 5 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.27 g (55%) as a brown semi-solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 461 Da., and microanalysis. - 172 - EXAMPLE 155 To 2,6-difluoroacetophenone (10.0 g, 64 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added aldehyde (13.46 g, 89.66 mmol). The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 18.27 g (99%) of an off-white solid which was identified by X H NMR. EXAMPLE 156 To the chalcone, 155. (10.0 g, 34.70 mmol) in absolute ethanol (40 mL) at 55°C was added acetic acid (4.0 mL) followed by slow addition of potassium cyanide (5.64 g, 86.73 mmol) in water (13 mL) . The solution was stirred at 100°C for 12 hours. The solution was cooled and treated with water (20 mL) . A gummy solid precipitated, and the solvent decanted off. The gummy residue was dissolved in ethyl acetate (100 mL) , washed - 173 - with water (20 mL) , dried over MgS0 4 filter, evaporated, purified on 400 g of Si0 2 (20% ethyl ace ate/hexane) to give the nitrile 1.5 g (14%) as a brownish solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 157 To the nitrile, 156. (1.5 g, 4.75 mmol) was added methanol (20 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled. The solution was evaporated to dryness, added ether (20 mL) , precipitated out, filtered to collect, and dried. Purified on 200 g of Si0 2 (15% ethyl acetate/ hexane). This gave the ester 1.0 g (54%) as an off-' white solid which was identified by X H NMR. -174- EXAMPLE 158 3-Benzori.3!dioxol-5-yl-4-benzyl-5- (2.6-difluoro- phenyl) -5-hydroxy-5H-furan-2-one To methanol (5 mL) was added sodium metal (0.022 g, 0.94 mmol) and stirred to dissolve. To this was added benzaldehyde (0.091 g, 0.86 mmol) then the ester, 157. (0.3 g, 0.78 mmol). The mixture was heated to reflux for 5 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/ hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.20 g (60%) as an' off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 422 Da., and microanalysis. -175- EXAMPLE 159 3-Benzori.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (3-propoxybenzyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.030 g, 1.227 mmol) and stirred to dissolve. To this was added 3-O-propoxybenzaldehyde (0.184 g, 1.124 mmol) then the ester, 15., (0.35 g, 1.022 mmol). The mixture was heated to reflux for 12 hours. The solution was then treated with acetic acid (6 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 15% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.20 g (41%) as an off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. - 176 - EXAMPLE 160 3-BenzoT1.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4-pyridin-3-ylmethyl-5H-furan-2-one To methanol (5 mL) was added sodium metal (0.024 g, 1.05 mmol) and stirred to dissolve. To this was added 3-pyridylcarboxaldehyde (0.103 g, 0.964 mmol) then the ester, 15., (0.30 g, 0.876 mmol). The mixture was heated to reflux for 2 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.16 g (43%) as an off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 418 Da., and HPLC = 97%. -177- EXAMPLE 161 3-Benzor1.3!dioxol-5-yl-5-hydroxy-4-isoquinolin- 4-ylmethyl-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.024 g, 1.05 mmol) and stirred to dissolve. To this was added 3-isoquinolinylcarboxaldehyde (0.15 g, 0.964 mmol) then the ester, 15., (0.30 g, 0.876 mmol). The mixture was heated to reflux for 12 hours. ' The solution was then treated with acetic acid (5 mL) and refluxed an additional 8 hours. The solvents were removed by evaporation. The cirude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.12 g (29%) as an off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 468 Da., and HPLC = 99%. -178- EXAMPLE 162 3-BenzoT1.3!dioxol-5-yl-4-biphenyl-4-ylmethyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.024 g, 1.05 mmol) and stirred to dissolve. To this was added 4-phenylbenzaldehyde (0.176 g, 0.964 mmol) then the ester, 15, (0.30 g, 0.876 mmol). The mixture was heated to reflxix for 12 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 8 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.18 < (41%) as an off-white solid. The butenolide wias identified by X H NMR, IR, MS, [M + H] + - 493 Da., and HPLC = 97%. -179- EXAMPLE 163 4- (3-Allyloxy-4-methoxybenzyl) -3-benzori.31dioxol-5-yl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.04 g, 1.75 mmol) and stirred to dissolve. To this was added 3-allyloxy-4-methoxybenzaldehyde (0.30 g, 1.60 mmol) then the ester, 15., (0.50 g, 1.46 mmol) . The mixture was heated to reflux for 12 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.20 g (27%) as an off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 503 Da., and microanalysis. -180- EXAMPLE 164 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydrox - 4- (4-isoquinolinyl) -5- (4-methoxyphenyl) - . (+) - . monohydrochloride To 161 (0.050 g, 0.107 mmol) in dioxane (1 mL) at 50°C was added 0.026 mL of 4N HCl in dioxane (0.97 eq, 0.1036 mmol) . The solution stirred for 2 minutes then evaporated to dryness, dried in vacuo 15 minutes to give 0.06 g solid. The salt was identified by X H NMR, MS, [M + H] + = 468 Da. EXAMPLE 165 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) -5-hydroxy- 5- (4-methoxyphenyl) -4- (3-pyridinylmethyl) - . (+) -. monohvdrochloride To 160 (0.05 g, 0.12 mmol) in dioxane (1 mL) was added 4N HCl in dioxane (0.029 L) (0.97 g, - 181- 0.1161 mmol) . Stirred for 2 minutes then evaporated to dryness, dried in vacuo for 15 minutes to give 0.055 g (100%) of a solid. The salt was identified by MS, [M + H] + = 418 Da. EXAMPLE 166 2 (5H) -Furanone. 3- (3.5-dimethoxyphenyl) -5-hydrox - 5- (4-methoxyphenyl) -4- (3-pyridinylmethyl) - . (*) - . monohydrochloride To 133 (0.0524 g, 0.1208 mmol) in dioxane was added 4N HCl in dioxane (0.029 mL) (0.970 g, 0.1171 mmol) . Stirred for 2 minutes then evaporated to dryness, dried in vacuo to give 0.055 g (100%) of a solid which was identified by X H NMR, MS, [M + H] + = 434 Da. - 182 - EXAMPLE 167 To 4-methoxyacetophenone (14.84 g, 98.82 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added N-methylindolyl-3-carboxaldehyde (20 g, 125.66 mmol). The solution swirled while 10% sodium hydroxide (8 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 100 mL) . The solid was dried in vacuo giving 17.58 g (62%) of an off-white solid which was identified by X H NMR. EXAMPLE 168 To the chalcone, 167. (7.00 g, 24.0 mmol) in absolute ethanol (15 mL) at 55°C was added acetic acid (2.75 mL) followed by slow addition of potassium cyanide (3.90 g, 60.0 mmol) in water (15 mL) . The solution was stirred at 70°C for 12 hours. The solution was cooled and treated with water (30 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (2 x 50 mL) , air dried, and then dried in vacuo to give • 183 - the nitrile 5.22 g (68%) as a brownish solid, The nitrile was identified by X H NMR. EXAMPLE 169 To the nitrile, 168. (5.22 g, 16.40 mmol) was added methanol (40 mL) . The mixture was saturated with HCl (g) and heated to 80°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (20 mL) . The resultant solid was filtered to collect, washed with 80% methanol (100 mL) , purified on 3.00 g of Si0 2 , (30% ethyl acetate/hexane) , and dried in vacuo. This gave the ester 1.0 g (17%) as a white solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 170 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) -3- (1-methyl) - lH-indol-3-yl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (0.029 g, 1.25 mmol) and stirred to dissolve. To this -184- was added aldehyde (0.133 g, 1.25 mmol) then the ester, 169. (0.4 g, 1.14 mmol) . The mixture was heated to reflux for 5 hours. The solution was then treated with acetic acid 8 mL and refluxed an additional 12 hours. The solvents were removed by evaporation. The crude product was then purified by flash chromatography (170 g silica gel, 20% ethyl acetate/hexane) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.24 g (49%) as an off-white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 425 Da., and microanalysis. EXAMPLE 171 2-Butenoic acid. 2- (1.3-benzodioxol-5-yl)- 4- (4-methoxyphenyl) -4-oxo-3- (phenylmethyl) - . (Z) - . ion(l-) compd. with 2-hydroxy-N.N.N-triethanaminium (1:1) Compound 2J) (0.661 g, 1.59 mmol) was dissolved in methanol (20 mL) . Choline hydroxide 45% solution in methanol (0.43 mL, 1.55 mmol) was added, stirred for 5 minutes, then evaporated in vacuo. The oil was dissolved in water (20 mL) and lyophilized to afford (4.) as a yellow powder 0.66 g (80%) . The salt was identified by X H NMR, IR, MS, [M + H] + = 417 Da. - 185 - EXAMPLE 172 2-Butenoic acid. 2- (1.3-benzodioxol-5-yl) -3- T(4-methoxy-3-methylphenyl)methyl! -4- (4-methoxyphenyl) - 4-oxo- . (Z) - . ion(l-) compd. with 2-hydroxy-N.N.N-tri- methylethanaminium (1:1) To a solution of 89., (1.147 g, 2.50 mmol) in methanol (20 mL) and THF (4 mL) was added choline hydroxide in methanol (45%, by weight) (0.68 mL, 2.45 mmol), stirred for 5 minutes, then evaporated in vacuo. This oil was dissolved in water (200 mL) and washed with ether (50 mL) . Lyophilization of the aqueous layer afforded the salt 1.27 g (90%) . The salt was identified by X H NMR, MS [M + H] + = 417 Da. -186- EXAMPLE 173 2-Butenoic acid. 2- (1.3-benzodioxol-5-yl) -4- (methoxy- phenyl) -4-oxo-3- \ T4- (trifluoromethyl)phenyl!methyl! - . (Z) - . ion(l-) compd. with 2-hydroxy-N.N.N-trimethyi- ethanaminium (1:1) To a solution of J38., (0.048 g, 0.1 mmol) in methanol (2 mL) was added choline hydroxide in methanol (45%, by weight) (0.025 mL, 0.09 mmol). This solution was evaporated to afford a colorless viscous oil. This oil crystallized from methanol (0.5 mL) and ether (3 mL) . The product (2) was collected and washed with ether (2 x 10 mL) . Yield (0.046 g, 78%) mp 150-158 dec. The salt was identified by X H NMR, MS, [M + H] + = 441 Da. - 187- EXAMPLE 174 To p-methoxyacetophenone (5.0 g, 33 mmol) in absolute ethanol (9 mL) in an erlenmeyer was added 2-furaldehyde (2.73 mL) (33 mmol) . The solution swirled while 10% sodium hydroxide (1.5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 5.52 g (73%) of a solid which was identified by X H NMR, IR, MS, and inicroanalysis. To the chalcone, 174. (5.52 g, 24 mmol) in ethanol (50 mL) at 55°C was added acetic acid (1.92 mL) followed by slow addition of potassium cyanide (3.84 g, 59 mmol) in water (10 mL) . The solution was stirred at reflux for 1 hour. The solution was cooled and treated with water. The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 3.61 g (59%). The nitrile was identified by X H NMR, IR, and MS. - 188 - EXAMPLE 176 A mixture of 175 (1.0 g, 3.9 mmol), p-toluenesulfonic acid monohydrate (0.74 g, 3.9 mmol) in 20 mL MeOH was heated at reflux for 6 hours. No precipitate was formed. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated sodium chloride, dried MgS0 4 , filtered, and concentrated. The crude product was purified by flash chromatography (silica gel 60, 7:3 hexane:ethyl acetate) to give a light yellow viscous oil 0.52 g (46%) . The product was identified by X H NMR, MS, and X3 C NMR. EXAMPLE 177 4'-Benzyl-5 '-hydroxy-5 '- (4-methoxyphenyl) - 5 • H- T2.3'!bifuranyl-2'-one To methanol (5 mL) was added sodium metal (44 mg, 1.9 mmol) and stirred to dissolve. To this was added benzaldehyde (0.20 mL, 2.0 mmol) then the ester, 176. (051 g, 1.8 mmol) . The mixture was heated to reflux -189- for 4 hours. The solution was then treated with acetic acid (5.0 mL) and refluxed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 7:3 hexane:ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.46 g (71%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 363 Da., and microanalysis. EXAMPLE 178 To 4-methoxyacetophenone (5.0 g, 33 mmol) in absolute ethanol (15 mL) in an erlenmeyer was added 2-thiophenecarboxaldehyde (3.08 mL, 33 mmol). The solution swirled while 10% sodium hydroxide (15 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 5.34 g (66%) of a solid which was identified by X H NMR, IR, and MS. -190- EXAMPLE 179 To the chalcone, 178. (5.34 g, 22 mmol) in ethanol (50 mL) at 55°C was added acetic acid (1.74 mL) followed by slow addition of potassium cyanide (3.51 g, 54 mmol) in water (8 mL) . The solution was stirred at reflux for 1 hour. The mixture was concentrated in vacuo and partitioned between ethyl acetate and water. The organic layer was washed thoroughly with water, brine, and dried over MgS0 4 . The crude material was purified by silica gel chromatography (7:3 ethyl acetate:hexane) to give an oil 4.38 g (73%) . The nitrile was identified by X H NMR, MS, and IR. EXAMPLE 180 A solution of 179 (4.33 g, 16 mmol), p-toluenesulfonic acid monohydrate (3.04 g, 0.016 mmol) in 80 mL MeOH was heated at reflux for 6 hours. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated salt solution, dried (MgS0 4 ) , filtered, and concentrated. The crude product was purified by flash chromatography • 191- (silica gel 60, 7:3 hexane:ethyl acetate) to give a yellow viscous oil 3.18 g (65%). The product was identified by X H NMR and MS. EXAMPLE 181 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) -3-thiophen-2-yl- 5H-furan-2-one To methanol (15 mL) was added sodium metal (250 mg, 11 mmol) and stirred to dissolve. To this was added benzaldehyde (1.16 mL, 11.6 mmol) then the ester, 180. (3.18 g, 10.4 mmol). The mixture was heated to reflxix for 3.5 hours. The solution was then treated with acetic acid (10 mL) and reflxixed for an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 7:3 hexane:ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.65 g (16.5%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 379 Da., and microanalysis. - 192 - EXAMPLE 182 4- T4-BenzoTl.3!dioxol-5-yl-2-hydroxy-2- (4-methoxy¬ phenyl) -5-oxo-2.5-dihydrofuran-3-ylmethyl!benzoic acid methyl ester To methanol (5 mL) was added sodium metal (56 g, 2.4 mmol) and stirred to dissolve. To this was added methyl-4-formylbenzoate (415 mg, 2.5 mmol) then the ester, IJ., (0.8 g, 2.3 mmol). The mixture was heated to reflux for 1.5 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 3:2 hexane:ethyl acetate). The butenolide was isolated by evaporation of the appropriate fractions to give 0.63 g (57%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -193- EXAMPLE 183 To 4-methoxyacetophenone (5.0 g, 33 mmol) in absolute ethanol (9 mL) in an erlenmeyer was added 3-furaldehyde (2.9 mL, 33 mmol). The solution swirled while 10% sodium hydroxide (15 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 5.52 g (73%) of a solid which was identified by X H NMR and MS. EXAMPLE 184 To the chalcone, 183. (5.52 g, 2.4 mmol) in ethanol (50 mL) at 55°C was added acetic acid (1.92 mL) followed by slow addition of potassium cyanide (3.84 g, 59 mmol) in water (10 mL) . The solution was stirred at reflxix for 1 hour. The mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The organic layer was washed thoroughly with water, brine, and dried over MgS0 4 . The organic layer evaporated and the material purified by recrystallization from ethyl acetate\hexane to give - 194 - the nitrile 3.60 g (59%). The product identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 185 A solution of 184 (3.0 g, 0.012 mmol), p-toluenesulfonic acid monohydrate (2.82 g, 0.012 mmol) in 60 mL MeOH was heated at reflux for 6 hours. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgS0 4 ) , filtered, and concentrated. The crude product was purified by flash chromatography (silica gel 60, 7:3 hexane:ethyl acetate) to give a light yellow oil which crystallized on standing, 2.18 g (63%). The product was identified by X H NMR and MS. EXAMPLE 186 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl-5H- r3,3'1 - bifuranyl-2-one To methanol (20 mL) was added sodixmi metal (175 mg, 7.6 mmol) and stirred to dissolve. To this - 195 - was added benzaldehyde (0.80 g, 8.0 mmol) then the ester, 185. (2.07 g, 7.2 mmol). The mixture was heated to reflux for 2 hours. The solution was then treated with acetic acid (20 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 4:1 hexane:ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.64 g (25%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 363 Da., and microanalysis. EXAMPLE 187 To 3' ,4'-dimethoxyacetophenone (12.5 g, 69 mmol) in absolute ethanol (200 mL) in an erlenmeyer was added piperonal (10 g, 67 mmol) . The solution was swirled while 10% sodixπn hydroxide (35 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (50 mL) . The solid was dried in vacuo giving 18.3 g (87%) of a yellow solid which was identified by X H NMR, IR, MS, and microanalysis. -196- ΞXAMPLE 188 To the chalcone, 187. (17.95 g, 54.7) mmol) in 2-ethoxyethanol (150 mL) at 55°C was added acetic acid (4 mL) followed by slow addition of potassium cyanide (5.3 g, 81 mmol) in water. The solution was stirred at 105°C for 0.25 hour. The solution was cooled and treated with water (25 mL) . The mixture was filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (50 mL) , air dried, and then dried in vacuo to give the nitrile 12.7 g (68%) as a yellow solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 189 To the nitrile, 188. (10 g, 29.4 mmol) was added methanol (150 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (200 mL) . The resultant solid was filtered to collect, washed with 80% methanol (50 mL) , and dried in vacuo. This gave the ester 8.9 g - 197 - (81%) as a white solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 190 3-BenzoT1.31dioxol-5-yl-4-benzyl-5- (3.4-dimethoxy¬ phenyl) -5-hydroxy-5H-furan-2-one To methanol (100 mL) was added sodium metal (0.9 g, 39 mmol) and stirred to dissolve. To this was added benzaldehyde (4 g, 37 mmol) then the ester, 189. (8.3 g, 22.3 mmol). The mixture was heated to reflxix for 4 hours. The solution was then treated with acetic acid (18 mL) and refluxed an additional 16 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (25 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (1000 g silica gel, (10:1) CHCl 3 /ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 4.7 g (47%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 447 Da., and microanalysis. - 198- EXAMPLE 191 To 3' ,4' -dichloroactophenone (12.6 g, 69 mmol) in absolute ethanol (200 mL) in an erlenmeyer was added piperonal (10 g, 67 mmol) . The solution swirled while 10% sodium hydroxide (35 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (50 mL) . The solid was dried in vacuo giving 17.8 g (86%) of a yellow solid which was identified by X H NMR and MS. EXAMPLE 192 To the chalcone, 191. (17.3 g, 54 mmol) in 2-ethoxyethanol (150 mL) at 55°C was added acetic acid (3.5 mL) followed by slow addition of potassium cyanide (5.3 g, 81 mmol) in water (5 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was cooled and treated with water (15 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (50 mL) , air dried, and then dried in vacuo to give the nitrile 16.7 g -199- (89%) as a yellow solid. The nitrile was identified by X H NMR. EXAMPLE 193 To the nitrile, 192. (10 g, 28.8 mmol) was added methanol (200 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and removed the solvent. This gave the ester 10.2 g (98%) as a brown oil which was identified by X H NMR. EXAMPLE 194 3-BenzoTl.3!dioxol-5-yl-4-benzyl-5- (3,4-dichloro- phenyl) -5-hydroxy-5H-furan-2-one To methanol (100 mL) was added sodium metal (0.65 g, 28 mmol) and stirred to dissolve. To this was added benzaldehyde (3 g, 28 mmol) then the ester, 193. -200- (8.6 g, 22.5 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (20 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (25 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (1000 g silica gel, (10:1) CHCl 3 /ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 3.6 g (35%) as an orange solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 457 Da., and microanalysis. EXAMPLE 195 To 4'-cyanoacetophenone (9.7 g, 67 mmol) in absolute ethanol (200 mL) in an erlenmeyer was added piperonal (10 g, 67 mmol) . The solution swirled while 10% sodium hydroxide (35 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (50 mL) . The solid was dried in vacuo giving 13.5 g (73%) of a yellow solid which was identified by X H NMR, IR, MS, and microanalysis. - 201- EXAMPLE 196 To the chalcone, 195. (12.5 g, 45.8 mmol) in 2-ethoxyethanol (50 mL) at 55°C was added acetic acid (3.5 mL) followed by slow addition of potassium cyanide (7.5 g, 115 mmol) in water (10 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was cooled and treated with water (10 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (50 mL) , air dried, and then dried in vacuo to give the nitrile 8.6 g (62%) as a yellow solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 197 To the nitrile, 196. (6.2 g, 20.3 mmol) was added methanol (50 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (100 mL) . The resultant solid was filtered to collect, washed with 80% methanol -202 - (50 mL) , and dried in vacuo. This gave the ester 6.1 g (81%) as a light brown solid which was identified by X H NMR. EXAMPLE 198 4- (4-BenzoT1.3!dioxol-5-yl-3-benzyl-2-hydroxy-5-oxo- 2.5-dihydrofuran-2-yl)benzoic acid methyl ester To methanol (50 mL) was added sodium metal (0.2 g, 8.7 mmol) and stirred to dissolve. To this was added benzaldehyde (0.6 g, 5.7 mmol) then the ester, 197. (1.5 g, 4 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (100 mL) and water (20 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (300 g silica gel, (10:1) CHCl 3 /ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.85 g (48%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 445 Da., and microanalysis. -203- EXAMPLE 199 4- T4-BenzoT1.31dioxol-5-yl-3-benzyl-2-hydroxy-5-oxo- 2.5-dihydrofuran-2-yl) -benzoic acid To the butenolide, 198. (0.5 g, 1.1 mmol) was dissolved in methanol (10 mL) added 1.1 mL of IN NaOH at 0°C, then at room temperature for 1 hour. The solvent was removed by evaporation. The residue was dissolved in water (15 mL) and acidified with IN HCl (15 mL) , filtered the solid dried xinder vacuo to give the acid 0.35 g (74% yield) as a white solid. The acid was identified by X H NMR, IR, MS, [M + H] + = 431 Da., and microanalysis. EXAMPLE 200 To 4' -hydroxyacetophenone (9.1 g, 69 mmol) in absolute ethanol (200 mL) in an erlenmeyer was added -204 - piperonal (10 g, 67 mmol) . The solution swirled while 10% sodium hydroxide (35 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (50 mL) . The solid was dried in vacuo giving 16.5 g (91%) of a yellow solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 201 A mixture of chalcone, 200. (5.35 g, 19.7 mmol), K 2 C0 3 (3 g, 20 mmol) , and isopropyl bromide (3 g, 24 mmol) in 100 mL of DMF was heated to reflxix for 3 hours. The solvent was removed by evaporation. The residue was purified by flash column chromatography (1000 g silica gel, (200:1) CHCl 3 /ethyl acetate) . The product was isolated by evaporation of the appropriate fraction to give 4.8 g (78.5% yield) . The product was identified by X H NMR, IR, MS, [M + H] + - 311.1 Da., and microanalysis. -205 - EXAMPLE 202 To the chalcone, 201. (4.0 g, 12.9 mmol) in 2-ethoxyethanol (50 mL) at 55°C was added acetic acid (1 mL) followed by slow addition of potassium cyanide (1.3 g, 1.994 mmol) in water (1 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was cooled and treated with water (50 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (50 mL) , air dried, and then dried in vacuo to give the nitrile 3.85 g (88.6%) as a brown solid. The nitrile was identified by X H NMR and MS. EXAMPLE 203 To the nitrile, 202. (3 g, 8.9 mmol) was added methanol (25 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (100 mL) . The resultant solid was filtered to collect, washed with 80% methanol -206 - (10 mL) and dried in vacuo. This gave the ester 2.4 g (73%) as a yellow solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 204 3-Benzori.3!dioxol-5-yl-4-benzyl-5-hydroxy- 5- (4-isopropylphenyl) -5H-furan-2-one To methanol (60 mL) was added sodixim metal (0.15 g, 4.5 mmol) and stirred to dissolve. To this was added benzaldehyde (1 g, 9.4 mmol) then the ester, 203. (1.5 g, 4 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (100 mL) and water (20 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (300 g silica gel, (100:1) CHCl 3 /ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.46 g (26%) as a -207- white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 445 Da., and microanalysis. EXAMPLE 205 A mixture of chalcone, 200. (5.25 g, 19.6 mmol), K 2 C0 3 (3 g, 20 mmol), and benzylbromide (3.4 g, 20 mmol) in 100 mL of DMF was heated to reflxix for 3 hours. The solvent was removed by evaporation. The residue was purified by flash column chromatography (1000 g silica gel, (200:1) CHCl 3 /ethyl acetate) . The product was isolated by evaporation of the appropriate fractions to give 6.2 g (88% yield) . The product was identified by X H NMR, IR, MS, [M + H] + = 359.1 Da., and microanalysis. EXAMPLE 206 To the chalcone, 205 , (5.3 g, 14.8 mmol) in 2-ethoxyethanol (100 mL) at 55°C was added acetic acid (1.5 mL) followed by slow addition of potassium cyanide (2.7 g, 41.5 mmol) in water (1.5 mL) . The solution was stirred at 105°C for 0.25 hour. The solution was cooled and treated with water (25 mL) . The mixture was -208 - then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (50 mL) , air dried, and then dried in vacuo to give the nitrile 4.7 g (82.5%) as a brown solid. The nitrile was identified by X H NMR and MS. EXAMPLE 207 To the nitrile, 206. (3.4 g, 8.8 mmol) was added methanol (25 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (100 mL) . The resultant solid was filtered to collect, washed with 80% methanol (20 mL) and dried in vacuo. This gave the ester 2.7 g (73%) as a white solid which was identified by X H NMR, IR, MS, and microanalysis. -209- EXAMPLE 208 3-Benzori.3!dioxol-5-yl-4-benzyl-5- (4-benzyloxy- pheny1) -5-hydroxy-5H-furan-2-one To methanol (50 mL) was added sodium metal (0.15 g, 4.5 mmol) and stirred to dissolve. To this was added benzaldehyde (1 g, 9.4 mmol) then the ester, 207. (1.5 g, 3.6 mmol). The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (100 mL) and water (20 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (300 g silica gel, (100:1) CHCl 3 /ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.96 g (54%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 493 Da., and microanalysis. -210 - EXAMPLE 209 To 3'4' -dimethylacetophenone (11.5 g, 77.6 mmol) in absolute ethanol (200 mL) in an erlenmeyer was added piperonal (10 g, 67 mmol) . The solution swirled while 10% sodium hydroxide (35. mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (100 mL) . The solid was dried in vacuo giving 18.6 g (99%) of a light yellow solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 210 The chalcone, 209. (17.61 g, 62.9 mmol) in 2-ethoxyethanol (200 mL) at 55°C was added acetic acid (4 mL) followed by slow addition of KCN (5.7 g, 87.7 mmol) in water (6 mL) . The solution was stirred at 105°C for 0.25 hour. The solvent was evaporated. The residue was purified by flash column chromatography (1.5 kg silica gel, CHC1 3 ) . The product was isolated by evaporation of the appropriate fractions to give -211- 19.08 g (98% yield) as a brown oil which was identified by X H NMR. EXAMPLE 211 To the nitrile, 209. (12.5 g, 40.67 mmol) was added methanol (50 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (100 mL) and ethyl acetate (100 mL) . The organic phase was separated and dried over MgS0 4 and evaporated. The crude product was purified by flash column chromatography (1000 g silica gel, (200:1) CHCl 3 /ethyl acetate) . The product was isolated by evaporation of the appropriate fractions to give the ester 11.2 g (81%) as a brown oil which was identified by X H NMR. -212 - EXAMPLE 212 3-BenzoT1.3!dioxol-5-yl-4-benzyl-5- (3.4-dimethyl- phenyl) -5-hydroxy-5H-furan-2-one To methanol (60 mL) was added sodium metal (0.5 g, 22 mmol) and stirred to dissolve. To this was " added benzaldehyde (2.6 g, 24.5 mmol) then the ester, 211. (5.6 g, 16.5 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (10 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (200 mL) and water (25 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (1000 g silica gel, (100:1) CHCl 3 /ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 4.6 g (67%) as an orange solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 415 Da., and microanalysis. -213 - EXAMPLE 213 To o-methylacetophenone (10.1 g, 75 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added piperonal (15 g, 100 mmol) . The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. No solid. The mixture was evaporated in vacuo and the residue partitioned between ethyl acetate and water. The organic phase washed with saturated NaHC0 3 , 10% citric acid, and brine. The organic phase dried over magnesium sulfate and evaporated and used as is. EXAMPLE 214 To the chalcone, 213. (24.5 g, 92 mmol) in ethanol (350 mL) at 55°C was added acetic acid (11.4 mL) followed by slow addition of potassium cyanide (15 g, 230 mmol) in water (60 mL) . The solution was stirred at 60°C for 18 hours. The solution was cooled and treated with water (150 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried -214 - in vacuo to give the nitrile 18.5 g (69%) as a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 215 To the nitrile, 214. (3.8 g, 12.95 mmol) was added methanol (50 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (70 mL) . The mixture was evaporated in vacuo and partitioned between water and ethyl acetate. The organic phase washed with brine and dried over magnesium sulfate. The organic phase was evaporated in vacuo. This gave the ester 3.7 g (88%) as a foam which was identified by X H NMR, IR, MS, and microanalysis. -215- EXAMPLE 216 3-BenzoTl.3!dioxol-5-yl-4-benzyl-5-hydroxy-5-o-tolyl- 5H-furan-2-one To methanol (12 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 mg, 4.4 mmol) then the ester, 215. (1.31 g, 4.0 mmol) . The mixture was heated to reflux for 4.5 hours. The solution was then treated with acetic acid (1.5 mL) and refluxed an additional 16 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (70 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (200 g silica gel, 5% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 305 mg (19%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 401 Da., and microanalysis. -216 - EXAMPLE 217 To m-methoxyacetophenone (11.3 g, 75 mmol) in absolute ethanol (30 mL) in an erlenmeyer was added piperonal (13.5 g, 90 mmol). The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 19.35 g (92%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 218 To the chalcone, 217. (17.85 g, 63.2 mmol) in ethanol (300 mL) at 55°C was added acetic acid (7.6 mL) followed by slow addition of potassium cyanide (10.29 g, 158 mmol) in water (50 mL) . The solution was stirred at 75-90°C for 24 hours. The solution was cooled and treated with water (100 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 17.7 g (91%) as a -217- solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 219 To the nitrile, 218. (17 g, 55 mmol) was added methanol (200 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (50 mL) . The compound oiled out of solution. The liquid phase was decanted off the oil and the oil partitioned between ethyl acetate and brine. The organic phase was dried over magnesium sulfate and evaporated in vacuo to give a foam. The ester 15.1 g (80%) was identified by X H NMR, IR, MS, and microanalysis. -218- EXAMPLE 220 3-BenzoTl.3!dioxol-5-yl-4-benzyl-5-hydroxy- 5- (3-methoxyphenyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 mg, 4.4 mmol) then the ester, 219. (1.37 g, 4.0 mmol) . The mixture was heated to reflxax for 4 hours. The solution was then treated with acetic acid (1.0 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (75 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (250 g silica gel, 5% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 545 mg (33%) as a light yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 417 Da., and microanalysis. -219- EXAMPLE 221 3-BenzoT1.3!dioxol-5-yl-4-cyclohexylmethyl-5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To ethanol (12 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added cyclohexanecarboxaldehyde (494 mg, 4.4 mmol) then the ester, ljJ, (1.37 g, 4.0 mmol) . The mixture was heated to reflxix for 90 hours. The solution was then treated with acetic acid (1.0 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the crude product was then purified by flash chromatography (150 g silica gel, 5-10% ethyl acetate/ methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 190 mg (11%) as a light yellow oil. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 417 Da., and microanalysis. -220- EXAMPLE 222 3-BenzoTl.31dioxol-5-yl-4-benzyl-5-methoxy- 5- (4-methoxyphenyl) -5H-furan-2-one To the butenolide, 2_Q, (205 mg, 0.5 mmol) in methanol (15 mL) was added HCl (g) . The saturated solution warmed to 50°C for 18 hours. The cooled solution was evaporated in vacuo and the product purified by chromatography (120 g silica gel, 3:1 hexane:ethyl acetate) . The appropriate fractions were combined and evaporated to give the new butenolide as a clear solid, 119 mg (55%) . The compound was identified by X H NMR, IR, MS, [M + H] + = 431 Da., and microanalysis. -221- EXAMPLE 223 3-BenzoTl.3!dioxol-5-yl-4-benzyl-5- (4-methoxyphenyl) - 5H-furan-2-one In TFA (8 mL) , at 0°C, xinder an N 2 stream was added in parts a mixture of the butenolide (416 mg, 1.0 mmol) and sodium borohydride (378 mg, 10 mmol) . The resultant deep green solution was stirred for 5 minutes. The solution evaporated free of TFA and carefully treated with water (20 mL) . The solution extracted with ethyl acetate (25 mL) and the organic phase separated and washed with brine. The organic phase evaporated and the crude material purified by chromatography (70 g silica gel, 5% ethyl acetate/ methylene chloride) . The appropriate fractions were combined and evaporated in vacuo to give the new butenolide as a yellow solid, 282 mg (70%) . The butenolide was identified by X H NMR, Ir, MS, [M + H] + = 401 Da., and microanalysis. - 222 - EXAMPLE 224 To m-methylacetophenone (10.06 g, 75 mmol) in absolute ethanol (30 mL) in an erlenmeyer was added piperonal (13.50 g, 90 mmol). The solution swirled while 10% sodium, hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 100 mL) . The solid was dried in vacuo giving 19.1 g (96%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 225 To the chalcone, 224. (16.0 g, 60 mmol) in ethanol (300 mL) at 55°C was added acetic acid (8.1 mL) followed by slow addition of potassium cyanide (9.8 g, 150 mmol) in water (50 mL) . The solution was stirred at 70°C for 24 hours. The solution was cooled and treated with water (125 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (200 mL) , air dried, and then dried in vacuo to give the nitrile 15.1 g (86%) as -223 - a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 226 To the nitrile, 225. (10 g, 34.1 mmol) was added methanol (120 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (30 mL) . The resultant solid was filtered to collect, washed with 80% methanol, and dried in vacuo. This gave the ester 6.7 g (60%) as a tan solid which was identified by X H NMR, IR, MS, and microanalysis. -224- EXAMPLE 227 3-BenzoTl.31dioxol-5-yl-4-benzyl-5-hydroxy-5-m-tolyl- 5H-furan-2-one To methanol (12 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 mg, 4.4 mmol) then the ester, 226. (1.31 g, 4.0 mmol) . The mixture was heated to reflux for 6 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 5% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 980 mg (61%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 401 Da., and microanalysis. -225- EXAMPLE 228 To p-methoxyacetophenone (10.5 g, 70 mmol) in absolute ethanol (65 mL) in an erlenmeyer was added 3,4,5-trimethoxybenzaldehyde (16.7 g, 85 mmol). The solution swirled while 10% sodium hydroxide (3 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 22.4 g (97%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 229 To the chalcone, 228. (13.93 g, 42.4 mmol) in ethanol (250 L) at 55°C was added acetic acid (5.8 mL) followed by slow addition of potassium cyanide (6.9 g, 106 mmol) in water (50 mL) . The mixture treated with chloroform (50 mL) . The solution was stirred at 60°C for 24 hours. The mixture treated with an additional amoxint of potassium cyanide (6.9 g, 106 mmol) and -226- acetic acid (5.8 g) and warmed to reflux, stirred 24 hours. The reaction mixture evaporated free of solvents and the aqueous extracted with ethyl acetate. The organic phase washed with 10% citric acid (75 mL) , saturated sodium bicarbonate (75 mL) , and brine (75 mL) . The organic phase was dried over magnesium sulfate and evaporated in vacuo to give an oil, 8.6 g (57%) . The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 230 To the nitrile, 229. (8.3 g, 23.4 mmol) was added methanol (120 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (75 mL) . The resultant solid was filtered to collect, washed with 80% methanol, and dried in vacuo. This gave the ester 3.7 g (40%) as a tan solid which was identified by X H NMR, IR, MS, and microanalysis. -227- EXAMPLE 231 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 3- (3.4.5-trimethoxyphenyl) -5H-furan-2-one To methanol (12 mL) was added sodium metal (97 g, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 g, 4.4 mmol) then the ester, 230. (1.55 g, 4.0 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 8 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, (1:3) ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 690 mg (37%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 463 Da., and microanalysis. -228 - EXAMPLE 232 To m-chloroacetophenone (6.8 g, 50 mmol) in absolute ethanol (30 mL) in an erlenmeyer was added piperonal (10.1 g, 67.5 mmol). The solution swirled while 10% sodium hydroxide (32 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 12.7 g (89%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 233 To the chalcone, 232. (11.3 g, 39.4 mmol) in ethanol (300 mL) at 55°C was added acetic acid (4.7 mL) followed by slow addition of potassium cyanide (6.4 g, 98 mmol) in water (40 mL) . The solution was stirred at 60-70°C for 18 hours. The solution was cooled and treated with water (100 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 9.95 g (80%) as a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. -229- EXAMPLE 234 To the nitrile, 233. (9.65 g, 30.8 mmol) was added methanol (100 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (75 mL) . The resultant solid was filtered to collect, washed with 80% methanol, and dried in vacuo. This gave the ester 7.0 g (65%) as a solid which was identified by X H NMR, IR, MS, and microanalysis. -230- EXAMPLE 235 3-Benzon.3!dioxol-5-yl-4-benzyl-5- (3-chlorophenyl) - 5-hydroxy-5H-furan-2-one To methanol (12 mL) was added sodixmi metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 g, 4.4 mmol) then the ester, 234. (1.39 g, 4.0 mmol). The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (1.0 mL) and refluxed an additional 7 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (200 g silica gel, 5% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.1 g (65%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 421 Da., and microanalysis. -231- EXAMPLE 236 3-Benzori.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (4-methylsulfanylbenzyl) -5H-furan-2-one To methanol (25 mL) was added sodium metal (301 mg, 13.1 mmol) and stirred to dissolve. To this was added 4-thiomethylbenzaldehyde (2.09 g, 13.75 mmol) then the ester, 19., (4.48 g, 12.5 mmol). The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (75 mL) and water (75 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (100 g silica gel, 5% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 2.3 g (39%) as glass. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 463 Da., and microanalysis. -232- EXAMPLE 237 3-BenzoT1.3!dioxol-5-yl-5-hydroxy-4- (4-methanesulfonyl- benzyl) -5- (4-methoxyphenyl) -5H-furan-2-one In chloroform (45 mL) was dissolved the butenolide, 236. (735 mg, 1.54 mmol) and 50% m-chloroperbenzoic acid (1.38 g, 4.0 mmol). The solution warmed to 50°C for 24 hours. The mixture filtered free of insolubles and the organic filtrate washed successively with water (100 mL) , saturated NaHCo (40 mL) , and brine (40 mL) . The organic phase dried over magnesium sulfate and evaporated in vacuo. The crude material was purified by chromatography (150 g silica gel, 20% ethyl acetate/methylene chloride) . The appropriate fractions were combined and evaporated in vacuo to give a light yellow foam, 295 mg (38%) . The butenolide was identified by X H NMR, IR, MS, [M + H] + = 495, and microanalysis. -233 - EXAMPLE 238 To 2,4-dimethoxyacetophenone (12.6 g, 75 mmol) in absolute ethanol (50 mL) in an erlenmeyer was added piperonal (11.26 g, 75 mmol) . The solution swirled while 10% sodium hydroxide (3 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 100 mL) . The solid was dried in vacuo giving 21.1 g (96%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 239 To the chalcone, 238. (15.6 g, 50 mmol) in ethanol (300 mL) at 55°C was added acetic acid (7.0 mL) followed by slow addition of potassium cyanide (8.14 g, 125 mmol) in water (50 mL) . The solution was stirred at 70°C for 96 hours. The solution was cooled and -234- treated with water (100 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 9.9 g (58%) as a solid. The nitrile was identified by X H NMR, IR, and microanalysis. EXAMPLE 240 To the nitrile, 239. (9.06 g, 26.7 mmol) was added methanol (50 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (30 mL) . The resultant solid was filtered to collect, washed with 80% methanol (2 x 100 mL) and dried in vacuo. This gave the ester 4.9 g (49%) as a solid which was identified by X H NMR, IR, MS, and microanalysis. -235- EXAMPLE 241 3-BenzoT1.31dioxol-5-yl-4-benzyl-5- (2.4-dimethoxy¬ phenyl) -5-hydrox -5H-furan-2-one To methanol (12 mL) was added sodium metal (97 g, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 g, 4.4 mmol) then the ester, 240. (1.49 g, 4.0 mmol). The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 5% ethyl acetate/ methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 501 mg (28%) as a tan foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 447 Da., and microanalysis. -236 - EXAMPLE 242 To 3,4-methylenedioxyacetophenone (16.4 g, 100 mmol) in absolute ethanol (80 mL) in an erlenmeyer was added piperonal (16.5 g, 110 mmol) . The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 200 mL) . The solid was dried in vacuo giving 21.2 g (72%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 243 To the chalcone, 242. (20.85 g, 70.4 mmol) in ethanol (400 mL) at 55°C was added acetic acid (9.2 mL) followed by slow addition of potassium cyanide (11.45 g, 176 mmol) in water (50 mL) . The solution was stirred at reflxαx for 24 hours. The solution was cooled and treated with water (350 mL) . The mixture was then filtered to collect the solid. The solid was -237- washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 22.2 g (97%) . The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 244 To the nitrile, 243. (21.2 g, 65.6 mmol) was added methanol (150 mL) . The mixture was saturated with HCl (g) and heated to 45°C xintil no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (150 mL) . The resultant solid was filtered to collect, washed with 80% methanol (100 mL) , and dried in vacuo. This gave the ester 6.1 g (26%) as a solid which was identified by X H NMR, IR, MS, and microanalysis. -238- EXAMPLE 245 3.5-Bis-benzori.3!dioxol-5-yl-4-benzyl-5-hydroxy- 5H-furan-2-one To methanol (12 mL) was added sodixam metal (101 mg, 4.4 mmol) and stirred to dissolve. To this was added benzaldehyde (488 mg, 4.6 mmol) then the ester, 244. (1.43 g, 4.0 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (25 mL) and water (25 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 595 mg (35%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 431 Da., and microanalysis. -239- EXAMPLE 246 To o-methyoxyacetophenone (10.5 g, 70 mmol) in absolute ethanol (35 mL) in an erlenmeyer was added piperonal (11.26 g, 75 mmol) . The solution swirled while 10% sodium hydroxide (2 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 19.1 g (96%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 247 To the chalcone, 246. (18.3 g, 64.8 mmol) in ethanol (200 mL) at 55°C was added acetic acid (8.6 mL) followed by slow addition of potassium cyanide (10.5 g, 162 mmol) in water (20 mL) . The solution was stirred at 60°C for 18 hours. The solution was cooled and treated with water (120 mL) . The mixture was then filtered to collect the solid. The solid was washed -240- repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 11.55 g (58%). The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 248 To the nitrile, 247. (11.17 g, 36.1 mmol) was added methanol (125 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (120 mL) . The resultant solid was filtered to collect, washed with 80% methanol (2 x 100 mL) , and dried in vacuo. This gave the ester 7.7 g (63%) as a solid which was identified by X H NMR, IR, MS, and microanalysis. -241- EXAMPLE 249 3-BenzoT1.31dioxol-5-yl-4-benzyl-5-hydroxy- 5- (2-methoxyphenyl) -5H-furan-2-one To methanol (12 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 g, 4.4 mmol) then the ester, 248. (1.37 g, 4.0 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (75 mL) and water (75 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 5% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 605 mg (38%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 417 Da., and microanalysis. -242- EXAMPLE 250 3-Benzori.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4-naphthalen-1-ylmethyl-5H-furan-2-one To methanol (10 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 g, 4.4 mmol) then the ester, 19. (1.37 g, 4.0 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (30 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate/ methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.50 mg (80%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 467 Da., and microanalysis. -243- EXAMPLE 251 3-BenzoTl.3!dioxol-5-yl-5-hydroxy-4- (4-methoxy- 2.5-dimethylbenzyl) -5- (4-methoxyphenyl) -5H-furan-2-one To methanol (12 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added 2,5-dimethyl-4-methoxybenzaldehyde (722 mg, 4.4 mmol) then the ester, 19_, (1.37 g, 4.0 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (1.0 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 5% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 340 mg (18%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -244- EXAMPLE 252 TR-(R*.S*)1 and TS- (R*,R*)!carbamic acid. (1-phenylethyl) -. 4- (1.3-benzodioxol-5-yl)-2.5-dihydro- 2- (4-methyoxyphenyl) -5-oxo-3- (phenylmethyl) -2-furanyl ester In methylene chloride (5 mL) was dissolved the butenolide, 2j0, (416 mg, 1.0 mmol) and the solution treated with (S) -α-phenethylisocyanate (162 mg, 1.1 mmol) and the mix stirred at room temperature for 24 hours. The mixture treated with DMAP (15 mg) and again with (S) -α-phenethylisocyanate (162 mg, 1.1 mmol) . The solution stirred for an additional 24 hours and then quenched with water (20 mL) . The solution treated with ethyl acetate (10 mL) and the organic phase separated, dried over magnesium sulfate, and evaporated to give an oil. The oil was purified by flash chromatography (70 g silica gel, 2:1 hexane:ethyl acetate) . The new butenolide 310 mg (55%) was identified by X H NMR, IR, MS, [M + H] + = 564 Da., and microanalysis. -245- EXAMPLE 253 2-Butenoic acid. 2- (1.3-benzodioxol-5-yl) -4- (4-methoxy phenyl) -4-oxo-3- (3-propoxyphenyl) ethyl! - . (Z) -. ion(l-) compound with 2-hydroxy- N.N.N-trimethylethanaminium (1:1) The butenolide , 159. (5.0 g, 10.54 mmol) was dissolved in methanol (100 mL) and the solution treated with choline hydroxide (45% solution in methanol) (1.28 g, 10.54 mmol) . The solution stirred for 0.5 hour and evaporated in vacuo to give a foam. The foam was dissolved in water (150 mL) and washed once with ether (100 mL) . The aqueous solution was evaporated in vacuo free of organics, frozen, and lyophilized to give 5.2 g (87%) of the salt. The salt was identified by X H NMR, IR, MS, [M + H] + = 578 Da., and microanalysis. -246- EXAMPLE 254 3-BenzoTl.3!dioxol-5-yl-5-hydroxy-4- (4-methoxy-2.3- dimethylbenzyl) -5- (4-methoxyphenyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added 2,3-dimethyl-4-methoxybenzaldehyde (722 mg, 4.4 mmol) then the ester, 19., (1.37 g, 4.8 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (100 g silica gel, 10% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 198 mg (10%) as a pale yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -247- EXAMPLE 255 4- (3-Allyloxy-4-methoxybenzyl) -3-benzoTl.3!dioxol-5-yl- 5- (2.4-dimethoxypheny1) -5-hydrox -5H-furan-2-one To methanol (8 mL) was added sodium metal (101 mg, 4.4 mmol) and stirred to dissolve. To this was added 3-allyloxy-4-methoxybenzaldehyde (865 mg, 4.5 mmol) then the ester, 240. (1.61 g, 4.3 mmol) . The ' mixture was heated to reflxix for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 72 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 185 mg (8%) as light yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 533 Da., and microanalysis. -248- EXAMPLE 256 3-Benzon.3!dioxol-5-yl-4-benzyl-5- (4-chlorophenyl) - 5-hydroxy-1.5-dihydropyrrol-2-one A solution of 39 (100 mg, 0.228 mmol) in anhydrous THF (l mL) was treated with ammonium hydroxide (0.3 mL) , and the reaction mixture stirred for 2 hours at room temperature. The solvent was evaporated, the residue taken up in ethyl acetate, dried over magnesium sulfate, and the solvent evaporated. The resulting glass was crystallized from hexane/ethyl acetate to afford the product as brown crystals (80.0 mg, 83%)'. The product was characterized by X H NMR, MS, (M + H) = 420) , IR, and C NMR. -249- EXAMPLE 257 3-Benzori.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (2-phenoxybenzyl) -5H-furan-2-one To methanol 30 mL was added sodium metal (0.125 g, 5.46 mmol) and stirred to dissolve. To this was added O-phenoxybenzaldehyde (1.28 g, 6.4 mmol) then the ester, 19., (1.70 g, 4.96 mmol) . The mixture was heated to reflux for 6 hours. The solution was then treated with acetic acid 3 mL and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate 50 mL and water 25 mL. The organic phase was separated and dried over magnisium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (50 g silica gel, EtOAc/hexane = 25/75) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.78 g (70%) as a green foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 509 Da., and microanalysis. - 250 - EXAMPLE 258 To 4-methoxyacetophenone (10.5 g, 70 mmol) in absolute ethanol (40 mL) in an erlenmeyer was added 3,4-dimethoxybenzaldehyde (14.0 g, 90 mmol) . The solution swirled while 10% sodium hydroxide (4 mL) added. The mixture swirled for 10 minutes and allowed to stand. The solution evaporated to a small volume diluted with ethyl acetate (200 mL) and washed successively with 10% citric acid, saturated sodium bicarbonate (150 mL) , 15% sodium bisulfite (2 x 150 mL) , and brine (150 mL) . The organic phase dried over magnesium sulfate and evaporated in vacuo to give a thick oil 21.3 g (100%), which was identified by X H NMR, IR, MS, and microanalysis. -251- EXAMPLE 259 To the chalcone, 258. (16.2 g, 54.2 mmol) in ethanol (300 mL) at 55°C was added acetic acid (7.1 mL) followed by slow addition of potassium cyanide (8.84 g, 136 mmol) in water (50 mL) . The solution was stirred at 60°C for 24 hours. The solution was cooled and treated with water (250 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (100 mL) , air dried, .and then dried in vacuo to give the nitrile 11.3 g (64%) as a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. -252- EXAMPLE 260 To the nitrile, 259. (8.9 g, 27.4 mmol) was added methanol (110 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin-layer chromatography. The solution was cooled and treated with water (100 mL) . The product oils out and the liquid decanted from the oil. The oil was dissolved in ethyl acetate (150 mL) and washed with IN HCl (70 mL) . The organic phase washed with saturated sodium bicarbonate (100 mL) and brine (50 mL) . The organic phase dried over magnesium sulfate and evaporated in vacuo to give a thick oil 7.1 g (72%) which was identified by X H NMR, IR, MS, and microanalysis. -253- EXAMPLE 261 4-Benzyl-3- (3.4-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (12 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added benzaldehyde (467 mg, 4.4 mmol) then the ester, 260. (1.43 g, 4.0 mmol) . The mixture was heated to reflux for 6 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (175 g silica gel, 10% ethyl acetate/methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.980 g (57%) as a light green solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 433 Da., and microanalysis. -254- EXAMPLE 262 2H-Pyrrole-2-one. 3- (1.3-benzodioxol-5-yl) -1.5-dihydro- 5-hydroxy-4.5-bis(4-methoxyphenyl) - . (+) - Sixty percent sodium hydride (0.42 g, 10.5 mmol) in oil suspension was washed free of oil using dry THF. The resulting solid was suspended in 5 mL DMSO, heated briefly to 60°C, and stirred to a homogeneous brown oil over 1 hour at 25°C. This solution was dilutfed with 75 mL dry THF, and a solution of 3,4(methylenedioxy) - phenylacetonitrile (1.61 g, 10 mmol) in 25 mL THF was added. After 3 minutes at 25°C, 4,4'-dimethoxybenzil (2.7 g, 19 mmol) was added, followed by stirring at 25°C overnight. The solvents were removed by evaporation giving an orange oil which was partitioned between ethyl acetate (100 mL) and saturated sodium bicarbonate solution. The organic phase was washed with brine, dried over magnesium sulfate, and evaporated to dryness. The crude product was purified by flash chromatography (450 g silica gel, ethyl acetate/CHCl 3 = 10/90). The product was isolated by evaporation of appropriate fractions followed by recrystallization from ethyl ether, giving a yellow solid 1.04 g (24%). The product was identified by X H NMR, MS, and microanalysis. -255 - EXAMPLE 263 To 4' -ethylacetophenone (14 g, 94.5 mmol) in absolute ethanol (200 mL) in an erlenmeyer was added piperonal (14 g, 93.3 mmol). The solution swirled while 10% sodium hydroxide (41 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (50 mL) . The solid was dried in vacuo giving 21 g (80%) of an off-white solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 264 To the chalcone, 263. (10 g, 35.7 mmol) in 2-ethoxyethanol (75 mL) at 55°C was added acetic acid (3.5 mL) followed by slow addition of potassium cyanide (6 g, 92.3 mmol) in water (10 mL) . The solution was stirred at 105°C for 0.5 hour. The solution was cooled and treated with water (200 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol (100 mL) , air dried, and then dried in vacuo to give the nitrile 5.9 g (54%) as - 256 - a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 265 To the nitrile, 264. (5.6 g, 18.2 mmol) was added methanol (100 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin layer chromatography. The solution was cooled and treated with water (10 mL)., then removed the solvent, redissolved in CH 2 C1 (25 mL) , filtered through a short packed column to give methyl ester as an oil. This gave the ester 6.0 g (96%) as a brown oil which was identified by X H NMR. -257- EXAMPLE 266 3-Benzori.3!dioxol-5-yl-4-benzyl-5- (4-ethylphenyl) - 5-hydroxy-5H-furan-2-one To methanol (50 mL) was added sodium metal (0.75 g, 32.6 mmol) and stirred to dissolve. To this was added benzaldehyde (3 g, 18.7 mmol) then the ester 265. (5.42 g, 15.9 mmol). The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 0.5 hour. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (20 mL) . The organic phase was separated'and dried over magnesium sulfate and evaporated to dryness. The cirude product was then purified by flash chromatography (500 g silica gel, (10:1) CH 2 Cl 2 :ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.65 g (25%) as white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 415 Da., and microanalysis. -258- EXAMPLE 267 3- \4- (3.5-Dimethoxyphenyl) -2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydrofuran-3-ylmethyllbenzoic acid To 134 (100 mg, 0.217 mmol) in Acetone (10 mL) was added at 0°C Jones' Reagent (2.39 mmol) dropwise stirred at 0°C and monitored by TLC (30% EtOAc/hexane) . No starting material after 4 hours. The mixture was diluted with EtOAc (50 mL) then washed with H 2 0 (2 x 30 mL) , dried over MgS0 4 , filtered, evaporated in vacuo. Purified on Si0 2 (170 g) eluent (3% CH 3 0H/CH 2 C1 2 ) y: 0.03 g. NMR, IR, HPLC, 81%. EXAMPLE 268 To 4'-methylthioacetophenone (15.5 g, 93.3 mmol) in absolute ethanol (250 mL) in an erlenmeyer was added piperonal (14 g, 93.3 mmol). The solution swirled while 10% sodium hydroxide (41 mL) added. The mixture swirled for 10 minutes and allowed to stand to -259 - precipitate. The solid was collected by filtration and washed with 80% ethanol (50 mL) . The solid was dried in vacuo giving 27 g (97%) of a yellow solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 269 Triphenyl orthothioformate (6.8 g, 20 mmol) was treated with n-Buli (2.1 M, 10 mL) at -78°C under nitrogen for 30 minutes, then added the chalcone 268. (5.4 g, 18.1 mmol) in 100 mL of THF, another 30 minutes at -78°C, removed the dry ice bath stirred at room temperature for 30 minutes. The solution was treated with NH 4 C1 (saturated) (5 mL) , and passed a short packed silica gel column (200 g) , evaporated to dryness. The crude product was recrystallized in ethyl acetate/ether to give the white solid (7.2 g) , which was identified (62% yield) by H-NMR. EXAMPLE 270 To the orthothio ester 269. (3.7 g, 5.8 mmol), HgCl 2 (7.8 g, 28.7 mmol), HgO (2.5 g, 11.5 mmol) in 150 mL of EtOH (95%) was refluxed for 7 hours under -260- nitrogen. The mixture was filtered and the filtrate was diluted with H 2 0 (75 mL) and extracted with two 100 ml of CH 2 C1 2 . The extracts were combined, washed with IN HCl (200 mL) , brine, dried MgS0 4 . The crude product was purified by flash chromatography (500 g silica gel, (200:1) CH 2 Cl 2 /ethyl acetate). The ethyl ester was isolated by evaporation of the appropriate fraction to give 1.05 g (48.6% yield) which was identified by H-NMR. EXAMPLE 271 3-BenzoT1.3!dioxol-5-yl-4-benzyl-5-hydroxy-5- (4-methylsulfanylphenyl) -5H-furan-2-one To methanol (15 mL) was added sodium metal (0.2 g, 8.7 mmol) and stirred to dissolve. To this was added benzaldehyde (0.8 g, 7.5 mmol) then the ester, 270. (0.8 g, 2.1 mmol) . The mixture was heated to reflux for 3 hours. The solution was then treated with acetic acid (1 mL) and refluxed an additional 12 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (50 mL) and water (5 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (200 g silica gel, (20:1) CH 2 Cl 2 /ethyl acetate). The butenolide was isolated by evaporation of the appropriate fractions to give 0.28 g (31%) as white -261- solid. The butenolide was identified by X H NMR, IR, S, [M + H] + = 433 Da., and microanalysis. EXAMPLE 272 3- (3.5-Dimethoxyphenyl) -5-hydroxy-4- (4-methoxy- 3-methylbenzyl) -5- (4-methoxyphenyl-5H-furan-2-one To methanol (5 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 661 mg (4.4 mmol) 3-methyl-4-methoxy- beήzaldehyde. The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/ dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 550 mg (28.8%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 477 Da., and microanalysis. -262- EXAMPLE 273 3- (3.5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - 4- (4-methylbenzyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 529 mg (4.4 mmol) 4-methyl-benzaldehyde. The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 6 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 517 mg (28.9%) as a tan solid. The butenolide was identified by X H NMR, MS, [M + H] + = 447 Da., and microanalysis. -263- EXAMPLE 274 4- (4-Chlorobenzyl) -3- (3.5-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl-5H-furan-2-one To methanol (5 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 638 mg (4.4 mmol) 4-chloro-benzaldehyde. The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 6 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 900 mg (47.9%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 470 Da., and microanalysis. - 264 - EXAMPLE 275 2 (5H) -Furanone. 4- (cyclohexylmethyl) -3- (3.5- dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - To methanol (5 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 504 mg (4.4 mmol) cyclohexanecarbox¬ aldehyde. The mixture was heated to reflxix for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 36 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/ dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 513 mg (29.0%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 439 Da., and microanalysis. -265- EXAMPLE 276 3- (3.5-Dimethoxyphenyl) -5-hydroxy-4- (2-methoxybenzyl) - 5- (4-methoxyphenyl-5H-furan-2-one To methanol (5 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 611 mg (4.4 mmol) anisealdehyde. The mixture was heated to reflux for 36 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 36 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 644 mg (34.8%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 463 Da., and microanalysis. -266- EXAMPLE 277 3- (3.5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) - 4- (2-methylbenzyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 540 mg (4.4 mmol) O-toualdehyde. The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 585 mg (32.7%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 447 Da., and microanalysis. -267- EXAMPLE 278 4- (2-Chlorobenzy1) -3- (3.5-dimethoxyphenyl) -5-hydrox - 5- (4-methoxyphenyl) -5H-furan-2-one To methanol (5 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added a solution of the ester, 124. (1.43 g, 4.0 mmol) in 10 mL MeOH; and then 620 mg (4.4 mmol) O-chlorobenzaldehyde. The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate (150 mL) and water (150 mL) . The organic phase was separated and washed with brine and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g 230-400 mesh silica gel, eluting with 10% ethyl acetate/dichloromethane) . The butenolide was isolated by evaporation of the appropriate fractions to give 782 mg (41.6%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 470 Da., and microanalysis. -268- EXAMPLE 279 4- T4-BenzoTl.31dioxol-5-yl-2-hydroxy-2- (4-methoxy¬ phenyl) -5-oxo-2.5-dihydrofuran-3-ylmethyl!benzoic acid To a suspension of 182. 2.31 g (4.9 mmol) in methanol (30 mL) was added 9.8 mL of NaOH solution (1.0N) and the mixture warmed to reflux for 19 hours. The mixture diluted with water and washed once with ethyl acetate. The aqueous phase made acidic ' (pH = 2) with 1.0N HCl. The aqueous then extracted with ethyl acetate. The organic phase dried over magnesium sulfate, filtered, and evaporated to give an off white solid, 2.31 g (100%). The product was identified by X H NMR, IR, MS, [M + H] + = 461 and microanalysis. -269- EXAMPLE 280 1.3-Benzodioxol-5-acetic acid, o;- \2 - \ (4-carboxyphenyl) - methyl! -2- (4-methoxybenzoyl)ethylidene1 - . disodium salt To a solution of 279 0.27 g (0.59 mmol) in 5.0 mL MeOH was added dropwise 2.34 mL (1.17 mmol) 0.5017N NaOH solution in H 2 0. After addition was complete, the reaction mixture was stored overnight at room temperature. The reaction mixture was concentrated and the residue was lyophilized. Yield = ~300 mg. The co poxind was identified by X H NMR, IR, MS, [M + H] + = 460 Da., and microanalysis. -270- EXAMPLE 281 3-Benzofl.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (3.4.5-trimethoxybenzyl) -5H-furan-2-one To methanol 6 mL was added sodium metal 57 mg (2.5 mmol) and stirred to dissolve. To this was added 3,4,5-trimethoxybenzaldehyde 0.50 g (2.5 mmol) then the ester, 19_, 0.822 g (2.4 mmol). The mixture was heated to reflux for 16 hours. The solution was then treated with acetic acid 1.5 mL and refluxed for additional 6 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate 20 mL and water 20 mL. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by lash chromatography (150 g silica gel, 20% ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.719 g (59%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M+H] + = 507 Da., and microanalysis. -271- EXAMPLE 282 3-Benzoπ.3!dioxol-5-yl-4- (2-chlorobenzyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one To methanol 8 mL was added sodixim metal 97 mg (4.2 mmol) and stirred to dissolve. To this was added 2-chlorobenzaldehyde 0.619 g (4.4 mmol) then the ester, 19. 1.37 g (4.0 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid 1.0 mL and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate 25 mL and water 25 mL. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.925 g (51%) as a light yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 451 Da., and microanalysis. -272- EXAMPLE 283 3-Benzori.3!dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 4- (2-methylbenzyl) -5H-furan-2-one To methanol 15 mL was added sodium metal 97 mg (4.2 mmol) and stirred to dissolve. To this added 2-methylbenzaldehyde 529 mg (4.4 mmol) then the ester, 19. 1.37 g (4.0 mmol) . The mixture was heated to reflxix for 18 hours. The solution was then treated with acetic acid 1.0 mL and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate 50 mL and water 50 mL. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.30 g (76%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 431 Da., and microanalysis. -273- EXAMPLE 284 3-Benzori.31dioxol-5-yl-5-hydroxy-4- (2-methoxybenzyl) - 5- (4-methoxyphenyl) -5H-furan-2-one To methanol 8 mL was added sodium metal 97 mg (4.2 mmol) and stirred to dissolve. To this was added 2-methoxybenzaldehyde 0.599 g (4.4 mmol) then the ester, .12., 1.37 g (4.0 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid 1.0 mL and refluxed an additional 24 hours. The solvents were removed by evaporation and the residue was partitioned between ethyl acetate 25 mL and water 25 mL. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.730 g (40%) as a tan solid. The butenolide was identified by X H NMR, IR, MS, [M + S] + = 447 Da. for microanalysis. -274 - EXAMPLE 285 3-Benzo[1.31dioxol-5-yl-5-hydroxy-4.5-bis- (4-methoxyphenyl) -5H-furan-2-one Butyllithium in hexane (1.6 M, 6.25 mL, 10 mmol) was added to 50 mL dry tetrahydrofuran and cooled to -60°C. Diisopropylamine (1.4 mL, 10 mmol) was added, and the mixture was stirred for 30 minutes. 3,4- (Methylenedioxy)phenyl acetic acid (0.9 g, 5.0 mmol) dissolved in 20 mL dry tetrahydrofuran was added to the mixture was followed by stirred for 1 hour at 25°C. 4,4'-Dimethoxybenzil (1.35 g, 5.0 mmol) was added, followed by stirring at 25°C for 16 hours. The solvents were removed by evaporation giving a solid residue which was partitioned between ethyl acetate (75 mL) and IN citric acid. The organic phase was washed with brine, dried over magnesium sulfate, and evaporated to dryness. The crude product was purified by flash chromatography (50 g silica gel, ethyl acetate:hexane = 10:90). The product was isolated by evaporation of appropriate fractions giving a yellow solid 1.0 g. The solid was recrystallized from ethyl ether and pentane repeatedly, giving a yellow solid, 50 mg. This solid was further purified by flash chromatography (15 g silica gel, ethyl acetate:hexane = 10:90). The product was isolated by evaporation of appropriate fractions giving a yellow solid 21.3 mg (0.98%). The product was identified by X H NMR, MS, and microanalysis. -275- EXAMPLE 286 Benzoic acid. 3- \ \4- (1.3-benzodioxol-5-yl) - 2.5-dihydro-2-hydroxy-2- (4-methoxyphenyl) -5-oxo- 3-furanyl1methyl1 - . methyl ester To methanol (30 mL) was added sodium metal (0.3 g, 14.3 mmol) and stirred to dissolve. To this was added the ester, 19., (4.69 g, 13.7 mmol) then methyl- 3-formylbenzoate (2.45 g, 14.9 mmol). The mixture was heated to reflux for 3 hours. The solution was then treated with acetic acid (30 mL) and refluxed an additional 23 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 7:3 (hexane:ethyl acetate)). The butenolide was isolated by evaporation of the appropriate fractions to give 4.90 g (75%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -276 - EXAMPLE 287 To 3-methyl-4-methoxyacetophenone (7.2 g, 43.8 mmol) in absolute ethanol (30 mL) in an erlenmeyer was added piperonal (6.76 g, 45 mmol) . The solution swirled while 10% sodium hydroxide (2 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 11.9 g (92%) of a yellow solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 288 To the chalcone, 287. (5.77 g, 19.5 mmol) in ethanol (200 mL) at 55°C was added acetic acid (2.6 mL) followed by slow addition of potassium cyanide (3.17 g, 48.7 mmol) in water (30 mL) . The solution was stirred at reflux for 42 hours. The solution was cooled and treated with water (200 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 6.0 g (95%) as a dark -277- solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 289 To the nitrile, 288. (5.75 g, 17.8 mmol) was added methanol (70 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin layer chromatography. The solution was cooled and the liquid decanted from a thick oil. The oil was dissolved in ethyl acetate (100 mL) and washed with IN HCl (100 mL) , water (100 mL) , and brine (100 mL) . The organic phase dried over magnesium sulfate and evaporated in vacuo. The resultant oil was purified by Prep 500A chromatography (1 column, 8:3 (hexane:ethyl acetate) , 100 mL/min) . Evaporation of the correct fraction gave the ester 3.71 g (59%) as a thick oil which was identified by X H NMR, IR, MS, and microanalysis. -278- EXAMPLE 290 2 (5H) -Furanone. 3- (1.3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methoxy-3-methylphenyl) - - - (phenylmethyl) - . (+/-)- To methanol (8 mL) was added sodixαm metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 289. (1.4 g, 4.0 mmol) then benzaldehyde (467 mg, 4.4 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (1 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (25 mL) and water (20 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 5% ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 595 mg (35%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + - 431 Da., and microanalysis. -279- EXAMPLE 291 {4- r4-Benzori.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl! - phenyl}-acetic acid methyl ester To methanol (30 mL) was added sodium metal (0.19 g, 8.2 mmol) and stirred to dissolve. To this was added the ester, 19, (2.67 g, 7.8 mmol) then methyl- (4-formylphenyl)acetate (1.8 g, 10.1 mmol).. The mixture was heated to reflux for 2 hours. The solution was then treated with acetic acid (25 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 3:2 (hexane:ethyl acetate)). The butenolide was isolated by evaporation of the appropriate fractions to give 1.05 g (27%) as an oil. The butenolide was identified by X H NMR, IR, MS, [M + H] + - 489 Da., and it croanalysis. -280- EXAMPLE 292 3- r4-Benzori.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl] -benzoic acid A solution of 286. (3.0 g, 6.3 mmol) in methanol (30 mL) was treated with IN NaOH (12.6 mL) . The mixture was stirred at reflux for 47 hours. The mixture was evaporated to an aqueous mass which was diluted with water and washed with ethyl acetate. The organic washings were discarded, and the aqueous phase made acidic with concentrated HCl. This was extracted with ethyl acetate. The ethyl acetate washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo to give the butenolide 2.59 g (89%) of an off-white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 460 Da., and microanalysis. -281- EXAMPLE 293 {4- r4-Benzori.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 -phenyl}- acetic acid The butenolide was prepared as in 292 from 291. (0.87 g, 1.8 mmol). This gave 0.80 g (94%) of the butenolide as a white foam which was identified by X H NMR, IR, MS, [M + H] + = 474 Da., and microanalysis. -282- EXAMPLE 294 {3- r4-Benzori.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 - phenyl}-acetic acid methyl ester To methanol (30 mL) was added sodium metal (190 mg, 8.2 mmol) and stirred to dissolve. To this was added the ester, 19., (2.67 g, 7.8 mmol) then methyl- (3-formylphenyl)acetate (1.8 g, 10.1 mmol). The mixture was heated to reflux for 2 hours. The solution was then treated with acetic acid (30 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 7:3 (hexane:ethyl acetate)). The butenolide was isolated by evaporation of the appropriate fractions to give 0.52 g (14%) as a thick oil. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 489 Da., and microanalysis. -283- EXAMPLE 295 {3- r4-Benzori.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 - henyl}- acetic acid The butenolide was prepared as in 292 from 294, (0.29 g, 0.59 mmol) . This gave 0.27 g (96%) of the butenolide as a white foam which was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -284- ΞXAMPLE 296 3-BenzoTl.31dioxol-5-yl-5-hydroxy-4- (4-methoxy-3.5-dime thyl-benzyl) -5- (4-methoxy-phenyl) -5-H-furan-2-one To methanol (12 mL) was added sodium metal (99 mg, 4.3 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 3,5-dimethyl- 4-methoxybenzaldehyde (722 mg, 4.4 mmol). The mixture was heated to reflxix for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.03 g (55%) as a light yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -285 - EXAMPLE 297 3-BenzoTl.31dioxol-5-yl-4- (3.5-dimethyl-4-octyloxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (8 mL) was added sodium metal (55 mg, 2.4 mmol) and stirred to dissolve. To this was added the ester, 19., (0.79 g, 4.0 mmol) then 3,5-dimethyl- 4-ipropoxybenzaldehyde (480 mg, 2.5 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (1.5 mL) and refluxed ' an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and 10% citric acid (75 mL) . The organic phase washed with brine, separated, dried over magnesium sulfate, and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 313 mg (27%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 503 Da., and microanalysis. -286- EXAMPLE 298 To 4-methoxyacetophenone (15.0 g, 0.1 mmol) in absolute ethanol (100 mL) in an erlenmeyer was added 3-methoxy-4,5-methylenedioxybenzaldehyde (18.0 g, 0.1 mmol) . The solution swirled while 10% sodium hydroxide (8 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (2 x 200 mL) . The solid was dried in vacuo giving 27.2 g (87%) of a solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 299 To the chalcone, 298. (25.05 g, 80 mmol) in ethoxy ethanol (100 mL) at 55°C was added acetic acid (5.8 g) followed by slow addition of potassium cyanide (7.81 g, 120 mmol) in water (30 mL) . The solution was stirred at 105°C for 16 hours. The solution was cooled and treated with water (50 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 10% H 2 0:ethoxy ethanol (150 mL) , air -287- dried, and then dried in vacuo to give the nitrile 19.9 g (73%) as a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 300 To the nitrile, 299. (18.4 g, 54.2 mmol) was added methanol (100 mL) . The mixture was treated with p-toluenesulfonic acid (10.31 g, 54.2 mmol) and dioxane (50 mL) and warmed to reflux for 48 hours. The mixture was evaporated to a small volume and partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was dried over MgS0 4 , treated with charcoal, filtered, and evaporated in vacuo to give the ester as a wet foam 14.1 g (70%) which was identified by X H NMR, IR, MS, and microanalysis. -288- EXAMPLE 301 4-Benzyl-5-hydroxy-3- (7-methoxy-benzon.3]dioxol-5-yl) - 5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (12 mL) was added sodium metal (97 mg, 4.3 mmol) and stirred to dissolve. To this was added the ester, 300. (1.48 g, 4.0 mmol) then benzaldehyde (467 mg, 4.4 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 7% ethyl acetate: methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 518 mg (29%) as a light orange foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 447 Da., and microanalysis. -289- EXAMPLE 302 3-Benzof1.31dioxol-5-yl-4- (3.5-dimethyl-4-octyloxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (12 mL) was added sodixmi metal (97 g, 4.3 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 3,5-dimethyl- 4-n-octyloxybenzaldehyde (1.15 g, 4.4 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.985 g (43%) as an oily wax. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 573 Da., and microanalysis. -290- EXAMPLE 303 3-Benzori.31dioxol-5-yl-4- (3.5-dimethoxy-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (8 mL) was added sodium metal (97 mg, 4.3 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 3,5-dimethoxy- benzaldehyde (681 mg, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 7% ethyl acetate:me hylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 714 mg (37%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 477 Da., and microanalysis. -291- EXAMPLE 304 3-Benzon.31dioxol-5-yl-4- (3.4-dimethoxy-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (8 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 3,4-dimethoxy- benzaldehyde (681 mg, 4.1 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (7 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (30 mL) and water (30 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 15% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 655 mg (34%) as a beige foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 477 Da., and microanalysis. -292- EXAMPLE 305 3-Benzori.3ldioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) - 4- (2.3.4-trimethoxy-benzyl) -5H-furan-2-one To methanol (8 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was . added the ester, 1 , (1.37 g, 4.0 mmol) then 2,3,4-trimethoxybenzaldehyde (804 mg, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (175 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 819 mg (40%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 506 Da., and microanalysis. -293- EXAMPLE 306 3-Benzofl.31dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) - 4- (2.4.5-trimethoxy-benzyl) -5H-furan-2-one To methanol (8 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 2,4,5-trimethoxybenzaldehyde (804 mg, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 2-20% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 375 mg (18%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 507 Da., and microanalysis. -294- EXAMPLE 307 3-Benzori.31dioxol-5-yl-4- (2.5-dimethoxy-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (8 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19_, (1.37 g, 4.0 mmol) then 2,5-dimethoxy- benzaldehyde (681 mg, 4.1 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (100 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.15 g (60%) as a light yellow solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 477 Da., and microanalysis. -295- ΞXAMPLE 308 3-Benzo[1.31dioxol-5-yl-4- (2.3-dimethoxy-benzyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (8 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 2,3-dimethoxy- benzaldehyde (681 g, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 72 hours. The solvents were removed by ' evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.825 g (43%) as a thick oil. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 477 Da., and microanalysis. -296- EXAMPLE 309 3-Benzori.31dioxol-5-yl-4- (4-benzyloxy-3-methoxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (8 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 3-methoxy- 4-benzyloxybenzaldehyde (993 mg, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 72 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (70 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 710 mg (32%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 553 Da., and microanalysis. -297- EXAMPLE 310 3-Benzo[1.3ldioxol-5-yl-4- (6.6-dimethyl-bicyclor3.1.11 - hept-2-en-2-ylmethyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one To methanol (30 mL) was added sodium metal (0.074 g, 3.21 mmol) and stirred to dissolve. To this was added the ester, 19., (1.0 g, 2.92 mmol) then (IR) - (-)myrtenol (0.57 g, 3.76 mmol). The mixture was heated to reflux for 6 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 25 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (50 mL) and water (25 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then twice purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (10:90)). The butenolide was isolated by evaporation of the appropriate fractions to give 38 mg (2.8%) as a yellow solid. The butenolide was identified by X H NMR, MS, [M + H] + = 461 Da., and microanalysis. - 298 - EXAMPLE 311 2-Phenoxy-n-methyl. n-methoxybenzamide To o-phenoxybenzoic acid (50 g, 0.23 mol) in 500 mL CH 2 C1 2 was added carbonydii idazole (39 g, 0.24 mol) . The solution was stirred 1.5 hours at 25°C. A solution of 29 mL n-methylpiperidine (0.816 mol) and 0,N-dimethylhydroxylamine hydrochloride (22.77 g, 0.233 mol) in 300 mL CH 2 C1 2 was added. After stirring 24 hours at 25°C, the mixture was evaporated to an oil and resuspended in ethyl acetate. The solution was washed with IN citric acid, saturated NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo, 53.44 g, 93% yield. The amide was identified by X H NMR, MS, [M + H] + = 258 Da., and microanalysis. EXAMPLE 312 2- henoxybenzaldehyde To 111, (53.25 g, 0.206 mol) in 600 mL tetrahydrofuran at -10°C was added lithium aluminum -299 - hydride (10.16 g, 0.268 mol) over 5 minutes. The mixture was stirred at -5°C for 1 hour followed by the addition of a solution of sodium hydrogen sulfate, 75 g in 700 mL water. The pH was adjusted to 3 by the addition of 12% HCl solution, and the mixture was filtered. The filtrate was extracted with ethyl acetate, washed with NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo, 38 g. The crude oil was purified by flash chromatography (700 g silica gel, eluted with EtOAc:hexane (10:90)). Evaporation of the appropriate fractions gave an oil, 32 g, 78% yield. The aldehyde was identified by X H NMR, MS, [M + H] + = 197.2 Da., and microanalysis. EXAMPLE 313 3-BenzoTl.31dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) - 4- (2-phenoxy-benzyl) -5H-furan-2-one To methanol (30 mL) was added sodixim metal (0.125 g, 5.46 mmol) and stirred to dissolve. To this was added the ester, 19., (1.70 g, 4.96 mmol) then 2-phenoxybenzaldehyde (1.28 g, 6.4 mmol) . The mixture was heated to reflux for 6 hours. The solution was then treated with acetic acid (3 mL) and refluxed an -300 - additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (25:75) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.78 g (70%) as a pale green solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 509 Da., and microanalysis. EXAMPLE 314 3-Benzofl.31dioxol-5-yl-4-cyclopentylmethyl-5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (40 mL) was added sodix_tm metal (0.124 g, 5.42 mmol) and stirred to dissolve. To this was added the ester, 19., (1.69 g, 4.93 mmol) then cyclopentanal (0.60 g, 6.1 mmol) . The mixture was heated to reflxix for 48 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between EtOAc (40 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. - 301 - This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (10:90)). Evaporation of the appropriate fractions gave an oil which was crystallized from Et 2 0:hexane. This gave the butenolide 100 mg (5%) as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 409 Da., and microanalysis. EXAMPLE 315 3-Benzori.31dioxol-5-yl-4- (2-ethyl-butyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (40 mL) was added sodium metal (0.124 g, 5.42 mmol) and stirred to dissolve. To this was added the ester, 19, (1.69 g, 4.93 mmol) then 2-ethylbotyraldehyde (0.74 g, 7.39 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between EtOAc (40 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash - 302 - chromatography (50 g silica gel, eluted with EtOAc:hexane (10:90)). Evaporation of the appropriate fractions gave an oil which was crystallized from Et 2 0:pentane. This gave the butenolide 25 mg (1.23%) as a white solid. The butenolide was identified by X H NMR and microanalysis. EXAMPLE 316 3-BenzoTl.31dioxol-5-yl-4-cyclohex-3-enylmethyl- 5-hydroxy-5- (4-methox -phenyl) -5H-furan-2-one To methanol (35 mL) was added sodium metal (0.124 g, 5.42 mmol) and stirred to dissolve. To this was added the ester, .19, (1.68 g, 4.93 mmol) then 1,2,5,6-tetrahydrobenzaldehyde (0.81 g, 7.39 mmol). The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (50 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified -303- by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (10:90)). Evaporation of the appropriate fractions gave an oil which was crystallized from Et 2 0:pentane. This gave the butenolide 0.45 g (24%) as a solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 421 Da., and microanalysis. EXAMPLE 317 2-Cyclopentyl-2-phenyl-n-methyl. n-methoxyacetamide To 2-Cyclopentyl-2-phenylacetic acid (17 g, 0.083 mol) was added thionyl chloride (150 mL) . The solution was stirred 24 hours at 25°C. The solution was evaporated to an oil, 18.4 g. This was dissolved in 200 mL CH 2 C1 2 and cooled to -20°C. A solution of n-methylpiperidine (17.39 g, 0.174 mol) and 0,N-dimethylhydroxylamine hydrochloride (8.5 g, 0.087 mol) in 200 mL CH 2 C1 2 was added. After stirring for 24 hours at 25°C, the mixture was evaporated to a paste and resuspended in ethyl ether. The solution was washed with IN HCl, saturated NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo. The mixture was crystallized from cold hexane, 18.5 g recovered, 90% yield. The amide was identified by X H NMR, MS, [M + H] + = 248 Da., and microanalysis. -304- EXAMPLE 318 2-Cyclopentyl-2-phenylacetaldehyde To 112, (18.32 g, 0.074 mol) in 400 mL Et 2 0 at -40°C was added lithixim alximinum hydride (2.92 g, 0.077 mol) over 5 minutes. The mixture was stirred at 25°C for 6 hours followed by the addition of 125 mL 12% HCl. The organic phase was washed with NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo. The crude oil was purified by flash chromatography (120 g silica gel, eluted with hexane) . Evaporation of the appropriate fractions gave an oil, 11.2 g, 80% yield. The aldehyde was identified by X H NMR, MS, [M + H] + = 189 Da., and microanalysis. -305- EXAMPLE 319 3-Benzo[1.31dioxol-5-yl-4- (2-cyclopentyl-2-phenyl- ethyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (35 mL) was added sodium metal (0.074 g, 3.21 mmol) and stirred to dissolve. To this was added the ester, 19., (1.0 g, 2.92 mmol) then 2-cyclopentyl-2-phenylacetaldehyde (0.69 g, 3.65 mmol) . The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (50 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions from Et 2 0 gave a solid foam. This gave the butenolide 50 mg (3.4%) as a solid foam. The butenolide was identified by X H NMR, MS, [M + H] + = 499 Da., and microanalysis. -306- EXAMPLE 320 N-methyl. n-methoxy cyclohexylacetic acid To cyclohexylacetic acid (20 g, 0.14 mol) was added thionyl chloride (150 mL) . The solution was stirred 48 hours at 25°C. The solution was evaporated to an oil, 19.16 g. This was dissolved in 200 mL CH 2 C1 2 and cooled to 0°C. A solution of n-methyl¬ piperidine 25.45 g (0.255 mol) and 0,N-dimethyl- hydroxylamine hydrochloride (12.27 g, 0.125 mol) in 200 mL CH 2 C1 2 was added. After stirring 2 hours at 25°C, the mixture was evaporated to a paste and resuspended in ethyl ether. The solution was washed with IN HCl, saturated NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo, 24.57 g. The mixture was distilled at 0.75 mm Hg, bp 83-92°C, 18.73 g recovered, 85% yield. The amide was identified by X H NMR, MS, [M + H] + = 186 Da., and microanalysis. EXAMPLE 321 Cyclohexylacetaldehvde To 320. (18.46 g, 0.099 mol) in 400 mL Et 2 0 at -50°C was added lithium aluminum hydride (4.0 g, 0.104 mol) over 5 minutes. The mixture was stirred at -10°C for 3 hours followed by the addition of 125 mL - 307- 12% HCl. The organic phase was washed with NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo, 10.5 g. The crude oil (2.2 g) was purified by flash chromatography (50 g silica gel, eluted with hexane) . Evaporation of the appropriate fractions gave an oil, 0.75 g, 28% yield (prorated) . The aldehyde was used in the following reaction without further identification. EXAMPLE 322 3-Benzori.3ldioxol-5-yl-4- (2-cyclohexyl-ethyl) - 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (35 mL) was added sodium metal (0.124 g, 5.42 mmol) and stirred to dissolve. To this was added the ester, 19., (1.68 g, 4.93 mmol) then cyclohexylacetaldehyde 0.93 g (7.39 mmol) . The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (40 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash -308 - chromatography (50 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions gave an oil which was crystallized from Et 2 0:hexane. This gave the butenolide 0.149 g (6.9%) as a white solid. The butenolide was identified by X H NMR, MS, [M + H] + = 437 Da., and microanalysis. EXAMPLE 323 2- ( (3' .4' -Methylenedioxy)phenoxy)benzaldehyde To a solution of 60% NaH suspension (4 g, 0.1 mol) in 20 mL DMSO was added a .solution of sesamol (13.8 g, 0.1 mol) in 20 mL DMSO. The mixture was stirred at 25°C for 30 minutes, followed by the addition of 2-fluorobenzaldehyde (12.4 g, 0.1 mol) . The mixture was heated at 90°C for 3 hours. The mixture was cooled and poured into ice water and was extracted with ethyl ether. The organic phase was washed with brine, followed by charcoal filtration and drying over Na 2 S0 4 . The solution was evaporated to an oil in vacuo, which was purified by flash chromatography (600 g silica gel, eluted with EtOAc:hexane (20:80)). Evaporation of the appropriate fractions gave an oil, 3.35 g. The aldehyde was identified by X H NMR, MS, and microanalysis. -309- EXAMPLE 324 3-Benzon.31dioxol-5-yl-4- [2- (benzoTl.31dioxol- 5-yloxy) -benzyl! -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one To methanol (35 mL) was added sodium metal (0.074 g, 3.21 mmol) and stirred to dissolve. To this was added the ester, 19_, (1.0 g, 2.92 mmol) then 2- ( (3' ,4' -methylenedioxy)phenoxy)benzaldehyde (0.88 g, 3.65 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 3 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (50 mL) and IN sodium hydroxide (20 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions gave an oil which was crystallized from Et 2 0:hexane at -60°C. This gave the butenolide 0.145 g (9%) as a yellow solid. The butenolide was identified by X H NMR, MS, [M + H] + = 553 Da., and microanalysis. - 310 - EXAMPLE 325 2-Allyloxy. 4-methoxy acetophenone To 2-hydroxy-4-methoxy acetophenone (20 g, 120 mmol) in acetone (400 mL) was added allyl bromide (37 g, 300 mmol) followed by potassium carbonate (19 g, 132 mmol) . The mixture was heated to reflux for 30 hours, evaporated to an oil, and redissolved in ethyl ether. The solution was washed with IN NaOH, brine, and dried over MgS0 4 . The solution was evaporated to a solid and recrystallized from ' Et 2 0:hexane giving the acetophenone 16.02 g, 65% yield as a white solid. The acetophenone was identified by X H NMR, MS [M + H] + = 207 Da., and microanalysis. EXAMPLE 326 To 325. (16 g, 77.6 mmol) in absolute ethanol (50 mL) in an erlenmeyer was added piperonal (12.81 g, 85 mmol) . The solution swirled while 10% sodium hydroxide (5 mL) added. The mixture swirled for 3 hours and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (150 mL) . The solid was dried in vacuo giving 23.4 g -311- (89%) of a yellow solid which was identified by X H NMR, MS, and microanalysis. EXAMPLE 327 To the chalcone, 326. (23 g, 68 mmol) in absolute ethanol (400 mL) at 55°C was added acetic acid (8.8 mL) followed by slow addition of potassium cyanide (11 g, 167 mmol) in water (50 mL) . The solution was stirred at reflux for 24 hours. The solution was cooled and treated with water (150 mL) . The mixture was then filtered to collect the solid. The solid was filtered, redissolved in 750 mL ethyl acetate, filtered through charcoal, and evaporated to 0.5 volume. Addition of hexane gave the nitrile 17.1 g (69%) as a yellow solid. The nitrile was identified by X H NMR, MS, and microanalysis. EXAMPLE 328 To the nitrile, 327. (17 g, 46.9 mmol) was added methanol (40 mL) and dioxane (20 mL) , followed by p-toluenesulfonic acid (8.98 g, 46 mmol) . The mixture was heated at reflux for 24 hours, cooled, and - 312 - evaporated to a solid. The solid was suspended in ethyl acetate, filtered, washed with saturated NaHC0 3 , brine, and dried over MgS0 4 . The solution was evaporated to a solid which was filtered and recrystallized from ethyl acetate:hexane. This gave the ester 13.2 g (71%) as a yellow solid which was identified by X H NMR, MS, and microanalysis. EXAMPLE 329 3-Benzo[1.31dioxol-5-yl-5-methoχy-5- (4-methoxy-phenyl) - 4- (3.4.5-trimethoxy-benzyl) -5H-furan-2-one To methanol (60 mL) was added sodium metal (0.5 g, 26 mmol) and stirred to dissolve. To this was added the ester, 328. (6.84 g, 17.1 mmol) then benzaldehyde (2.76 g, 26 mmol) . The mixture was heated to reflux for 10 hours. The solution was then treated with acetic acid (9 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (150 mL) and IN sodium hydroxide (40 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 100 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The - 313 - crude butenolide was purified by flash chromatography (350 g silica gel, eluted with EtOAc:hexane (20:80)). Evaporation of the appropriate fractions from Et 2 0 gave a solid. This gave the butenolide 3.35 g (41%) as a white solid. The butenolide was identified by X H NMR, MS, [M + H] + = 473 Da., and microanalysis. EXAMPLE 330 3-Benzon.31dioxol-5-yl-4- (2-cyclohexyl-2-phenyl- ethyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To 281. (2.5 g, 4.93 mmol) in MeOH (100 mL) was added anhydrous HCl gas until the mixture had reached reflux. The mixture was heated at 70°C for 24 hours, and the solution was evaporated to a foam. The procedure was repeated, and the resulting foam was purified by flash chromatography (150 g silica gel, eluted with EtOAc:hexane (10:90) with a gradient to (20:80)). Evaporation of the appropriate fractions from Et 2 0 gave the butenolide, 1.85 g, 72% yield as a white solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 521 Da., and microanalysis. -314- EXAMPLE 331 2-Cyclohexyl-2-Phenyl-n-methyl. n-methoxyacetamide To 2-cyclohexyl-2-phenylacetic acid (14 g, 0.0645 mol) was added thionyl chloride (40 mL) . The solution was stirred 24 hours at 25°C. The solution was evaporated to an oil which was dissolved in 100 mL CH 2 C1 2 and cooled to -10°C. A solution of n-methyl¬ piperidine 14.75 g (0.134 mol) and 0,N-dimethyl- hydroxyla ine hydrochloride 6.48 g (0.0664 mol) in 300 mL CH 2 C1 2 was added. After stirring 5 hours at 25°C, the mixture was evaporated to a paste and resuspended in ethyl acetate. The solution was washed with IN HCl, saturated NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo, 17.14 g recovered. The amide was used without further purification in the following step. - 315 - EXAMPLE 332 2-Cyclohexyl-2-phenylacetaldehyde To 132, (16.8 g, 0.0644 mol) in 350 mL Et 2 0 at 0°C was added lithixim alximinum hydride (2.6 g, 0.0685 mol) over 5 minutes. The mixture was stirred at 25°C for 2 hours followed by the addition of 120 mL 12% HCl. The organic phase was washed with NaHC0 3 and brine, followed by drying over MgS0 4 . The solution was evaporated to an oil in vacuo. The crude oil was purified by flash chromatography (250 g silica gel, eluted with hexane) . Evaporation of the appropriate fractions gave an oil, 8.28 g, 63% yield. The aldehyde was identified by X H NMR, MS, [M + H] + = 203 Da., and microanalysis. -316- EXAMPLE 333 3-Benzo[1.31dioxol-5-yl-4- (2-cyclohexyl-2-phenyl- ethyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (40 mL) was added sodium metal (0.154 g, 6.42 mmol) and stirred to dissolve. To this was added the ester, 19., (2.0 g, 5.84 mmol) then 2-cyclohexyl-2-phenylacetaldehyde (1.48 g, 7.30 mmol). The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (6 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (70 mL) and IN sodium hydroxide (20 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The solution was evaporated to a solid which was purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions from Et 2 0 gave the butenolide 0.22 g (7.4%) as a white solid. The butenolide was identified by X H NMR, MS, [M + H] + - 513 Da., and microanalysis. -317 - EXAMPLE 334 To 4-methoxyacetophenone (8.05 g, 53.6 mmol) in denatured ethanol (35 mL) in an erlenmeyer was added 2-allyloxy-4-methoxybenzaldehyde (11.3 g, 58.8 mmol) . The solution swirled while 10% sodium hydroxide (4 mL) added. The mixture swirled for 4 hours and evaporated to a syrup. The mixture was redissolved in Et 2 0, washed with IN citric acid, saturated NaHC0 3 , brine, and dried over MgS0 4 . Concentration of the solution in vacuo gave a crystalline solid which was filtered. The solid was dried in vacuo giving 16.32 g (94%) of a yellow solid which was identified by X H NMR, MS, and microanalysis. EXAMPLE 335 To the chalcone, 334. (14 g, 43 mmol) in absolute EtOH (250 mL) at 55°C was added acetic acid (6.17 mL) followed by slow addition of potassium cyanide (7.68 g, 118 mmol) in water (30 mL) . The solution was stirred at reflux for 24 hours. The solution was cooled and - 318 - treated with water (150 mL) . The mixture was evaporated and the residue was dissolved in ethyl acetate. The solution was filtered and washed with IN citric acid, saturated NaHC0 3 , brine, and dried over MgS0 4 . The solution was evaporated to an oil which was suspended in Et 2 0, filtered through celite, and triturated with hexane giving a solid. The solid was dried in vacuo to give the nitrile 10.72 g (71%) as a solid. The nitrile was identified by X H NMR, MS, and microanalysis. EXAMPLE 336 To the nitrile, 335. (10.5 g, 27 mmol) was added methanol (25 mL) and dioxane (30 mL) , followed by p-toluenesulfonic acid (5.7 g, 30 mmol) . The mixture was heated at reflux for 18 hours, cooled, and evaporated to a solid. The solid was suspended in ethyl acetate, filtered, washed with saturated IN citric acid, NaHC0 3 , brine, and dried over MgS0 4 . The solution was evaporated to an oil which was purified by flash chromatography (400 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions from Et 2 0 gave the ester as an oil, 6.68 g, 58% yield, which was identified by X H NMR, MS, and microanalysis. -319- EXAMPLE 337 3- (2-Allyloxy-5-methoxy-phenyl) -4-benzyl-5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (55 mL) was added sodium metal (0.37 g, 160 mmol) and stirred to dissolve. To this was added the ester, 326. (4.8 g, 125 mmol) then benzaldehyde (2.01 g, 189 mmol) . The mixture was heated to reflux for 32 hours. The solution was then treated with acetic acid (10 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (75 mL) and IN sodium hydroxide (30 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 75 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The oil was crystallized from Et 2 0 and filtered. This gave the butenolide 3.6 g (63%) as a pale yellow solid. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 458 Da., and microanalysis. -320- EXAMPLE 338 {2- T4-Benzyl-5-hydroxy-5- (4-methoxy-phenyl) -2-oxo- 2.5-dihydro-furan-3-yll -4-methoxy-phenoxy}-acetic acid To the butenolide, 337. (3.3 g, 7.2 mmol) in dioxane (90 mL) was added a solution of 2.5% Os0 4 in 2-methyl-2-propanol (2.58 mL) . To this mixture was added a solution of NaI0 4 (6.5 g, 30 mmol) in 40 mL water. After stirring at 25°C for 6 hours, the mixture was evaporated, resuspended in ethyl acetate, filtered, washed with brine, and dried over MgS0 4 . The solution was evaporated to a foam (2.84 g) and purified by flash chromatography (150 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions gave a solid which was crystallized from Et 2 0, 0.997 g, 36% yield. The butenolide-aldehyde intermediate was identified by X H NMR, MS, [M + H] + = 461 Da., and microanalysis. To the butenolide-aldehyde intermediate (1.25 g, 2.71 mmol) in acetone (60 mL) was added 8N Jones reagent (1.0 mL) , followed by stirring for 45 minutes. Isopropyl alcohol (2 mL) was added, and the mixture was evaporated to a solid. The solid was purified by flash chromatography (50 g silica gel, eluted with a gradient of CHC1 3 to CHCl 3 :MeOH (5:95)). Evaporation of the appropriate fractions gave a solid, which was recrystallized from Et 2 0, 0.355 g, 27% yield as a - 321 - solid. The butenolide was identified by X H NMR, MS, [M + H] + - 476 Da., and microanalysis. EXAMPLE 339 3-BenzoT1.31dioxol-5-yl-4-cycloheptylmethy1-5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (40 mL) was added sodium metal (0.147 g, 6.42 mmol) and stirred to dissolve. To this was added the ester, 19., (2.0 g, 5.84 mmol) then cycloheptylaldehyde (110 mg, 8.76 mmol). The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (50 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions from Et 2 0 gave an oil which solidified. This gave the butenolide 121 mg (4.7%) as a solid. The -322 - butenolide was identified by X H NMR, MS, [M + H] + 437 Da., and microanalysis. EXAMPLE 340 3-Benzori.31dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) - 4-penty1-5H-furan-2-one To methanol (40 mL) was added sodium metal (0.147 g, 6.42 mmol) and stirred to dissolve. To this was added the ester, 19_, (2.0 g, 5.84 mmol) then valeraldehyde (0.93 g, 8.76 mmol). The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (40 mL) and IN sodium hydroxide (15 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 50 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude butenolide was purified by flash chromatography (50 g silica gel, eluted with EtOAc:hexane (5:95)). Evaporation of the appropriate fractions from Et 2 0 gave an oil. This gave the butenolide 264 mg (1.14%) as an oil. The butenolide -323 - was identified by X H NMR, MS, [M + H] + = 397.2 Da., and microanalysis. EXAMPLE 341 T2- (4-Benzo[1.31dioxol-5-yl-3-benzyl-2-hydroxy-5-oxo- 2.5-dihydro-furan-2-yl) -5-methoxy-phenoxy1 -acetic acid To the butenolide 329. (2.74 g, 6.19 mmol) in dioxane (50 mL) was added a solution of 2.5% 0s0 4 in 2-methyl-2-propanol (1.65 mL) . To this mixture was added a solution of NaI0 4 (4.14 g, 19.3 mmol) in 15 mL water. As the mixture thickened, dioxane (20 mL) was added. After stirring at 25°C for 5 hours, the mixture was evaporated, resuspended in ethyl acetate, filtered, and washed with IN HCl, brine, and dried over MgS0 4 . The solution was evaporated to a foam (2.75 g) and purified by flash chromatography (250 g silica gel, eluted with EtOAc:hexane (10:90)). Evaporation of the appropriate fractions gave a solid which was crystallized from Et 2 0, 1.03 g, 34% yield. The butenolide-aldehyde intermediate was identified by X H NMR, MS, [M + H] + = 475 Da., and microanalysis. To the butenolide-aldehyde intermediate (1.12 g, 2.36 mmol) in acetone (50 mL) was added 8N Jones reagent (0.87 mL) , followed by stirring for 45 minutes. Isopropyl alcohol (3 mL) was added, and the mixture was evaporated to an oil. The mixture was dissolved in -324 - CHC1 3 , washed with brine, and dried over MgS0 4 . The solution was evaporated to 5 mL in volume and purified by flash chromatography (50 g silica gel, eluted with a gradient of CHC1 3 to CHCl 3 :MeOH (5:95)). Evaporation of the appropriate fractions gave an oil, which was recrystallized from Et 2 0, 0.493 g, 42% yield as a solid. The butenolide was identified by X H NMR, MS, [M + H] + = 491 Da., and microanalysis. EXAMPLE 342 2-Allyloxy. 4-methoxybenzaldehyde To 2-hydroxy-4-methoxybenzaldehyde (25 g, 164 mmol) in acetone (500 mL) was added allyl bromide (49.6 g, 410 mmol) followed by potassium carbonate (34 g, 246 mmol) . The mixture was heated to reflux for 24 hours, filtered, evaporated to an oil, and redissolved in ethyl ether. The solution was washed with IN NaOH, IN HCl, brine, and dried over MgS0 4 . The solution was evaporated to a solid and recrystallized from Et 2 0:hexane giving the aldehyde 14.54 g, 46% yield as a white solid. The acetophenone was identified by X H NMR, MS, [M + H] + = 193 Da., and microanalysis. -325- EXAMPLE 343 4- (2-Allyloxy-4-methoxy-benzyl) -3-benzoTl.31dioxol-5-yl -5-hvdroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (40 mL) was added sodium metal (0.295 g, 128 mmol) and stirred to dissolve. To this was added the ester, 19_, (4.0 g, 117 mmol) then 342 (2.92 g, 150 mmol). The mixture was heated to reflux for 8 hours. The solution was then treated with acetic acid (9 mL) and refluxed an additional 5 hours. The solvents were removed by evaporation, and the residue was partitioned between ether (100 mL) and IN sodium hydroxide (30 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 75 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude oil was purified by flash chromatography (350 g silica gel, eluted with EtOAc:hexane (20:80)). Evaporation of the appropriate fractions gave the butenolide 0.72 g (12.5%) as a solid. The butenolide was identified by X H NMR, MS, [M + H] + = 503 Da., and microanalysis. -326- EXAMPLE 344 {2- r4-Benzori.3ldioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 -5-methoxy- phenoxy}-acetic acid To the butenolide, 343. (2.86 g, 5.69 mmol) in dioxane (70 mL) was added a solution of 2.5% 0s0 4 in 2-methyl-2-propanol (2.15 mL). To this mixture was added a solution of NaI0 4 (5 g, 23.3 mmol) in 28 mL water. After stirring at 25°C for 5.5 hours, the mixture was evaporated, resuspended in ethyl acetate, filtered, and washed with IN HCl, saturated NaHC0 3 , brine, and dried over MgS0 4 . The solution was evaporated to a foam (2.83 g) and purified by flash chromatography (150 g silica gel, eluted with EtOAc:hexane (10:90)). Evaporation of the appropriate fractions gave a solid which was evaporated to a foam from Et 2 0, 1.72 g, 60% yield. The butenolide-aldehyde intermediate was identified by X H NMR, MS, [M + H] + = 505.2 Da., and microanalysis. To the butenolide-aldehyde intermediate (1.60 g, 3.27 mmol) in acetone (70 mL) was added 8N Jones reagent (1.2 mL) , followed by stirring for 45 minutes. Isopropyl alcohol (2 mL) was added, and the mixture was evaporated to a solid. The mixture was evaporated, -327- resuspended in ethyl acetate, filtered, washed with brine, and dried over MgS0 4 . The solution was evaporated to a foam (1.6 g) . The solid was purified by flash chromatography (75 g silica gel, eluted with a gradient of CHC1 3 to CHCl 3 :MeOH (5:95)). Evaporation of the appropriate fractions gave a solid, which was recrystallized from Et 2 0, 0.374 g, 23% yield. The butenolide was identified by X H NMR, MS, [M + H] + = 521 Da., and microanalysis. EXAMPLE 345 To 4- (1-Imadazol)acetophenone (13.0 g, 70 mmol) in absolute ethanol (400 mL) in an erlenmeyer was added piperonal (12.01 g, 80 mmol) . The solution swirled while 10% sodium hydroxide (3 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol. The solid was dried in vacuo giving 18.3 g (82%) of a solid, which was identified by X H NMR, IR, MS, and microanalysis. -328- EXAMPLE 346 To the chalcone, 345. (17.7 g, 55.6 mmol) in ethanol (400 mL) at 55°C was added acetic acid (7.5 g) followed by slow addition of potassium cyanide (9.1 g, 140 mmol) in water. The solution was stirred at reflux for 18 hours. The solution was cooled and treated with water (200 mL) . The mixture was then filtered to collect the solid. The solid was washed repeatedly with 70% ethanol, air dried, and then dried in vacuo to give the nitrile 13.3 g (69%) as a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 347 To the nitrile, 346. (10.8 g, 31.3 mmol) was added methanol (80 mL) . The mixture was saturated with HCl (g) and heated to 45°C until no nitrile remained, by thin layer chromatography. The solution was cooled and treated with water (70 mL) . The resultant solid was filtered to collect, washed with 10% methanol (50 mL) , and dried in vacuo. This gave the ester 4.0 g - 329 - (34%) as a dark solid, which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 348 2-Butenoic acid. 2- (1.3-benzodioxol-5-yl) -4- T4- (1H-i idazol-1-yl)phenyl14-oxo-3- (phenylmethyl) - To methanol (12 mL) was added sodium metal (101 mg, 4.4 mmol) and stirred to dissolve. To this was added the ester, 347. (1.52 g, 4.0 mmol) then benzaldehyde (467 mg, 4.4 mmol) . The mixture was heated to reflux for 120 hours. The solution was then treated with acetic acid (1 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (50 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (140 g silica gel, 5% methanol:methylene chloride) . The crude butenolide was combined with a second run of above and further purified by silica gel chromatography (200 g silica gel, 3% methanol:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 221 mg (6%) as a yellow foam. The -330- butenolide was identified by X H NMR, IR, MS, [M + H] 452 Da., and microanalysis. EXAMPLE 349 2-Benzo ri .3l dioxol-5-yl-4- (4 -me thoxy -phenyl) -3 - f4- (2-morpholin-4-yl-ethylcarbamoyl) -benzyll -4-oxo-but- 2-enoic acid In DMF (12 mL) was dissolved, 279. (1.52 g, 3.3 mmol), and HOBt (459 mg, 3.4 mmol). To this was added N- (2-aminoethyl)morpholine (456 mg, 3.5 mmol) and DCC (702 mg, 3.4 mmol). The mixture stirred at room temperature overnight. The mixture filtered free of precipitate, and the filtrate evaporated free of DMF. The residue was dissolved in ethyl acetate (75 mL) and washed successively with water, saturated sodium bicarbonate, and brine (100 mL each) . The organic phase was evaporated in vacuo to give a foam. The butenolide was purified by chromatography (250 g silica gel, 5% methanol:methylene chloride) . Evaporation of the appropriate fractions gave 695 mg (37%) of the butenolide which was identified by X H NMR, MS, [M + H] + = 571, IR, and microanalysis. -331- EXAMPLE 350 HCl Benzamide. 4- \ \4- (1.3-benzodioxol-5-yl) - 2,5-dihydro-2-hydroxy-2- (4-methoxyphenyl) - 5-oxo-3-furanyl!methyl! -N- \2 - (4-morpholinyl)ethyl! - . monohydrochloride. (+/-)- In dioxane (5 mL) was dissolved 349. (519 mg, 0.90 mmol) , and the solution treated with a 4N HCl solution in dioxane (225 μL, 0.9 mmol). The mixture stirred for 5 minutes and evaporated in vacuo to give the butenolide as a white solid 535 mg (97%) . The butenolide was identified by X H NMR, IR, MS, [M + H] + 610 Da., and microanalysis. -332- EXAMPLE 351 Sodixim 2-benzo[1.31dioxol-5-yl-3-benzyl-4- (4-methoxyphenyl) -4-oxobut-2-enoate The butenolide, 0, (6.6 g, 15.8 mmol) was dissolved in methanol (150 mL) and treated with 0.4930N sodium hydroxide (aqueous), 31.8 mL (15.7 mmol). The solution stirred for 0.25 hours and evaporated free of methanol. The residue was partitioned between ether (200 mL) and distilled water (200 mL) . The ether discarded and the aqueous evaporated free of residual organic solvents, frozen, and lyophilized to give the butenolide salt as a white solid, 6.41 g (93%) . This was identified by X H NMR, IR, MS, [M + H] + = 417 Da., and microanalysis. -333- EXAMPLE 352 1.3-Benzodioxol-5-acetic acid, a- [2- (4-methoxyphenyl) 1- 1 \4- (1-methylethoxy)phenyl!methyl! -2-oxoethylene! - . 1Z) choline salt The butenolide, .84, (2.4 g, 5.06 mmol) was dissolved in methanol (75 mL) and treated with a solution of choline hydroxide in methanol (1.36 g of 45%, 5.06 mmol). The mixture evaporated free of methanol an dissolved in distilled water (100 mL) . The aqueous solution was evaporated free of residual methanol, frozen, and lyophilized. This gave the butenolide, 2.55 g (87%), as a hygroscopic white solid which was identified by X H NMR, IR, MS, [M + H] + = 475 Da., and microanalysis. -334- EXAMPLE 353 Sodixim 2-Benzo[1.3!dioxol-5-yl-3- (4-isopropoxy-benzyl) - 4- (4-methoxy-phenyl) -4-oxo-but-2-enoate The butenolide, .84., (4.0 g, 8.42 mmol) was dissolved in methanol (70 mL) and treated with 0.493N sodium hydroxide (aqueous) , 16.2 mL (8.0 mmol). The solution stirred for 5 minutes and evaporated in vacuo free of methanol. The residue was partitioned between ether (50 mL) and distilled water (100 mL) . The aqueous layer was separated, evaporated free of residual solvents, frozen, and lyophilized. This gave the butenolide salt, 2.53 g (64%), which was identified by X H NMR, MS, [M + H] + = 475 Da., and microanalysis. -335- EXAMPLE 354 Sodium 2-Benzori.3!dioxol-5-yl-4- (4-methoxy-phenyl) - 4-OXO-3- (3.4.5-trimethoxy-benzyl) -but-2-enoate The butenolide, 281. (4.04 g, 7.97 mmol) was dissolved in methanol (100 mL) and treated with 0.493N sodium hydroxide (aqueous), 15.8 mL (7.8 mmol). The solution stirred for 5 minutes and evaporated in vacuo to give a paste. The paste was partitioned between ether (100 mL) and distilled water (100 mL) . The aqueous phase was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave 3.65 g (88%) of the salt which was identified by X H NMR, IR, MS, [M + H] + = 505 Da., and microanalysis. -336- EXAMPLE 355 Sodium 2-Benzoπ.3!dioxol-5-yl-3-benzyl-4- (4-methoxy- 3-methyl-phenyl) -4-oxo-but-2-enoate The butenolide, 212. (5.2 g, 12.0 mmol) was dissolved in methanol (350 mL) and treated with I.OION sodium hydroxide (aqueous), 10.9 mL (11.0 mmol). The solution evaporated the residue partitioned between ether (250 mL) and distilled water (400 mL) . The aqueous phase was separated, evaporated free of residual organic solvents, frozen, and lyophilized. The butenolide salt, 4.45 g (89%), was identified by X H NMR, IR, MS, [M + H] + = 431 Da., and microanalysis. -337- EXAMPLE 356 5-Hvdroxy-3- (7-methoxy-benzof1.31dioxol-5-yl) -5- (4-methoxy-phenyl) -4- (3.4.5-trimethoxy-benzyl) -5H- furan-2-one To methanol (10 mL) was added sodixim metal (97 g, 4.2 mmol) and stirred to dissolve. To this was added the ester, 300. (1.48 g, 4.0 mmol) then 3,4,5-trimethoxybenzaldehyde (800 mg, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (4 mL) arid reflxixed an additional 72 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (75 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 20% ethyl acetate:methylene chloride) . The crude butenolide was isolated by evaporation of the appropriate fractions to give a foam. The foam was partitioned between ether (120 mL) and IN sodium hydroxide (40 mL) . The aqueous phase separated and acidified. The acid solution was extracted with ethyl acetate (2 x 50 mL) . The organic phases combined, -338- washed with brine, dried over magnesium sulfate, and evaporated in vacuo to give 610 mg (28%) as a yellow foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 537 Da., and microanalysis. EXAMPLE 357 To 3-methyl-4-methoxyacetophenone (34.4 g, 210 mmol) in absolute ethanol (120 mL) in an erlenmeyer was added 3-methoxypiperonal (38.6 g, 214 mmol). The solution swirled while 10% sodium hydroxide (12 mL) added. The mixture swirled for 10 minutes and allowed to stand to precipitate. The solid was collected by filtration and washed with 80% ethanol (3 x 300 mL) . The solid was dried in vacuo giving 45 g (65%) of an off-white solid which was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 358 To the chalcone, 357. (32.6 g, 100 mmol) in 2-ethoxyethanol (150 mL) at 55°C was added acetic acid (7.21 g) followed by slow addition of potassium cyanide - 339 - (9.8 g, 150 mmol) in water (30 mL) . The solution was stirred at 105°C for 18 hours. The solution was cooled then filtered to collect the solid. The solid was washed repeatedly with 10% water:ethoxyethanol (2 x 150 mL) , air dried, and then dried in vacuo to give the nitrile 29.5 g (84%) as a solid. The nitrile was identified by X H NMR, IR, MS, and microanalysis. EXAMPLE 359 To the nitrile, 358. (23.6 g, 66.8 mmol) was added methanol (150 mL) and dioxane (75 mL) , p-toluene- sulfonic acid hydrate (12.7 g, 66.8 mmol) . The mixture warmed to reflux and stirred 24 hours. The mixture cooled to room temperature and evaporated to dryness. The residue dissolved in ether (250 mL) and washed successively with water (200 mL) , saturated sodium bicarbonate (150 mL) , and brine (150 mL) . The ethereal solution treated with charcoal, dried, and evaporated to give 20.9 g (81%) of the ester which was identified by X H NMR, MS, [M + H] + = 387 Da. -340- EXAMPLE 360 4-Benzyl-5-hydroxy-3- (7-methoxy-benzo[1.3!dioxol-5-yl) - 5- (4-methoxy-3-methyl-phenyl) -5H-furan-2-one To methanol (10 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 359. (1.55 g, 4.0 mmol) then benzaldehyde (414 mg, 4.0 mmol) . The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (2 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (75 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica gel, 10% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give an oil. The oil was partitioned between ether (100 mL) and IN sodium hydroxide (25 mL) . The aqueous phase acidified with 6N HCl and extracted with ethyl acetate (2 x 25 mL) . The combined ethyl acetate layers dried over magnesium sulfate and evaporated in vacuo to give 520 mg (28%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 4£i Da., and microanalysis. -341- EXAMPLE 361 5-Hydroxy-3- (7-methoxy-benzofl.31dioxol-5-yl) -5- (4-methoxy-3-methyl-phenyl) -4- (3.4.5-trimethoxy¬ benzyl) -5H-furan-2-one To methanol (10 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 359. (1.55 g, 4.0 mmol) then 3,4,5-trimethoxybenzaldehyde (800 mg, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (100 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The solvents were evaporated and the residue dissolved in ether (150 mL) . This was extracted into IN sodium hydroxide (70 mL) . The aqueous phase separated, acidified, and extracted with ethyl acetate (2 x 75 mL) . The solvents were evaporated in vacuo to give an oil. The crude product was then purified by flash chromatography (150 g silica gel, 20% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the -342 appropriate fractions to give 279 mg (13%) as a white foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 551 Da., and microanalysis. EXAMPLE 362 {4- r4-Benzon.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 - 2.6-dimethoxy-phenoxy}-acetic acid ethyl ester To ethanol (10 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then 4- (ethylacetoxy) -3,5-dimethoxybenzaldehyde (1.10 g, 4.1 mmol) . The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (100 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (200 g silica gel, 20% ethyl - 343 - acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 356 mg (15%) as a thick oil. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 579 Da., and microanalysis. EXAMPLE 363 {5- r4-Benzori.3ldioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl! - 2.3-dimethoxy- henoxy}-acetic acid ethyl ester To ethanol (10 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19_, (1.37 g, 4.0 mmol) then 3- (ethyl- acetoxy) -4,5-dimethoxybenzaldehyde (1.10 g, 4.1 mmol). The mixture was heated to reflux for 18 hours. The solution was then treated with acetic acid (3 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (75 mL) and water (75 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (150 g silica -344- gel, 20% ethyl acetate:methylene chloride) . The butenolide was isolated by evaporation of the appropriate fractions to give 410 mg (18%) as an oil. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 579 Da., and microanalysis. EXAMPLE 364 {4- r4-Benzori.3]dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl! -2.6- dimethoxy-phenoxy}-acetic acid In methanol (5 mL) was dissolved the butenolide, 362. and the solution treated with I.OION sodium hydroxide (aqueous) 467 μL (0.471 mmol) . The mixture stirred 24 hours at room temperature and 24 hours at reflux. The mixture cooled to room temperature and evaporated to a paste. The paste partitioned between ethyl acetate (50 mL) and water (20 mL) . The aqueous phase acidified and extracted with fresh ethyl acetate. This ethyl acetate layer washed with brine and dried over magnesium sulfate. The solvents were evaporated in vacuo to give the butenolide 97 mg (37%) as a foam. The compound was identified by X H NMR, IR, MS, [M + H] + = 551 Da., and microanalysis. -345- EXAMPLE 365 {5- r4-Benzo[1.3!dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl! - 2.3-dimethoxy-phenoxy}-acetic acid In methanol (15 mL) was dissolved the butenolide, 363. and the solution treated with I.OION sodium hydroxide 1.13 mL (1.14 mmol) , and the solution warmed to reflxix for 24 hours. The mixture cooled to room temperature and evaporated free of methanol. The residue partitioned between water (50 mL) and ether (50 mL) . The aqueous phase separated and washed with ether (50 mL) and ethyl acetate (50 mL) . The aqueous phase was made acidic and extracted with fresh ethyl acetate (2 x 30 mL) . The combined final extraction phases evaporated in vacuo to give an oil, 295 mg (94%) . The butenolide was identified by X H NMR, IR, MS, [M + H] + = 551 Da., and microanalysis. -346- EXAMPLE 366 Potassium 3- (4-Acetylamino-benzyl) -2-benzo[1.3!dioxol- 5-yl-4- (4-methoxy-phenyl) -4-oxo-but-2-enoate The butenolide, .80., (917 mg, 1.94 mmol) was dissolved in methanol (25 mL) and treated with 1.018N potassium hydroxide (in methanol), (1.86 mL, 1.9 mmol). The solution was stirred for 5 minutes and evaporated free of methanol. The residue was partitioned between ether (100 mL) and distilled water (100 mL) . The aqueous solution was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave the butenolide salt 0.86 g (88%), which was identified by X H NMR, IR, MS, [M + H] + = 472 Da., and microanalysis. -347- EXAMPLE 367 Sodium 2-Benzofl.3!dioxol-5-yl-3- (4-methoxy-benzoyl) -4- (4-methoxy-2.5-dimethyl-phenyl) -but-2-enoate The butenolide, 251. (2.66 g, 5.60 mmol) was dissolved in methanol (100 mL) and treated with I.OION sodium hydroxide (aqueous), 5.26 mL (5.32 mmol). The solution was stirred for 5 minutes and evaporated free of methanol. The residue was partitioned between ether (200 mL) and distilled water (200 mL) . The aqueous solution was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave the butenolide salt 2.19 g (83%), which was identified by X H NMR, IR, MS, [M + H] + = 473 Da., and microanalysis. -348- EXAMPLE 368 Sodium 3-Benzyl-2- (7-methoxy-benzo[1.31dioxol-5-yl) - 4- (4-methoxy-phenyl) -4-oxo-but-2-enoate The butenolide, 301. (1.066 g, 2.39 mmol) was dissolved in methanol (25 mL) and treated with I.OION sodium hydroxide (aqueous), 2.20 mL (2.27 mmol). The solution was stirred for 10 minutes and evaporated free of methanol. The residue was partitioned between ether (100 mL) and distilled water (100 mL) . The aqueous solution was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave the butenolide salt 1.08 g (100%), which was identified by X H NMR, IR, MS, [M + H] + = 445 Da., and microanalysis. -349- EXAMPLE 369 Sodium 2- (7-Methoxy-benzo[1.31dioxol-5-yl) -3- (4-methoxy-3-methyl-benzoyl) -4- (3.4.5-trimethoxy- phenyl) -but-2-enoate The butenolide, 361. (3.0 g, 5.44 mmol) was dissolved in methanol (60 mL) and treated with I.OION sodium hydroxide (aqueous), 5.12 mL (5.17 mmol). The solution was stirred for 5 minutes and evaporated free of methanol. The residue was partitioned between ether (200 mL) and distilled water (120 mL) . The aqueous solution was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave the butenolide salt 2.91 g (98%), which was identified by X H NMR, IR, MS, [M + H] + = 549 Da., and microanalysis. -350- EXAMPLE 370 Sodium 3-Benzyl-2- (7-methoxy-benzori.3ldioxol-5-yl) - 4- (4-methoxy-3-methyl-phenyl) -4-oxo-but-2-enoate The butenolide, 360. (3.2 g, 6.95 mmol) was dissolved in methanol (60 mL) and treated with I.OION sodium hydroxide (aqueous), 6.5 mL (6.6 mmol). The solution was stirred for 2 minutes and evaporated free of methanol. The residue was partitioned between ether (150 mL) and distilled water (150 mL) . The aqueous solution was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave the butenolide salt 1.23 g (38%) , which was identified by X H NMR, IR, MS, [M + H] + = 459 Da., and microanalysis. -351- EXAMPLE 371 Sodium 2- (7-Methoxy-benzo[1.31dioxol-5-yl-4- (4-methoxy¬ phenyl) -4-OXO-3- (3.4.5-trimethoxy-benzyl) -but-2-enoate The butenolide, 356. (3.35 g, 6.2 mmol) was dissolved in methanol (60 mL) and treated with I.OION sodium hydroxide (aqueous), 5.87 mL (5.93 mmol). The solution was stirred for 3 minutes and evaporated free of methanol. The residue was partitioned between ether (200 mL) and distilled water (150 mL) . The aqueous ' solution was separated, evaporated free of residual organic solvents, frozen, and lyophilized. This gave the butenolide salt 3.1 g (94%) which was identified by X H NMR, IR, MS, [M + H] + = 535 Da., and microanalysis. -352- EXAMPLE 372 To 4-methoxyacetophenone (4.6 g, 30 mmol) in absolute ethanol (25 mL) in an erlenmeyer was added 2,5-dimethoxybenzaldehyde (6.84 g, 41.60 mmol) . The solution swirled while 10% sodium hydroxide (2 mL) added. The mixture stirred 1 hour (no precipitate) . EtOH evaporated, residue dissolved in EtOAc (200 mL) , and washed with H 2 0 (2 x 100 mL) and brine (100 mL) , then dried (MgS0 4 ) and stripped to 11.1 g crude yellow oil. Chromatographed (100% CH 2 C1 2 ) . Evaporation of appropriate fractions gave 6.5 g (73%) of a tan glass which was identified by X H NMR, MS, and microanalysis. EXAMPLE 373 To the chalcone, 372. (6.5 g, 21.79 mmol) in absolute ethanol (120 mL) at 55°C was added acetic acid (2.8 mL) followed by slow addition of potassium cyanide (3.55 g, 54.48 mmol) in water (25 mL) . The solution was stirred at reflux « 80°C for 24 hours. The solution was cooled and treated with water (150 mL) . The mixture was then decanted and the oily solid dissolved in 150 mL EtOAc and washed with brine -353 - (100 mL) ; then dried (MgS0 4 ) and evaporated to 6.02 g dark oily solid. Recrystallization from EtOAc:hexane to give the nitrile 2.78 g (39%) as a light green solid. The nitrile was identified by X H NMR and MS. EXAMPLE 374 To the nitrile, 373. (2.78 g, 8.55 mmol) was added methanol (50 mL) . The mixture was saturated with HCl (g) and heated to reflux until no nitrile remained, by thin layer chromatography. The solution was cooled and treated with water (50 mL) . Solution decanted away from the oily dark precipitate. Precipitate dissolved in 200 mL EtOAc and washed with H 2 0 (2 x 100 mL) and brine (100 mL) , then dried and evaporated to the ester 2.75 g (90%) as a green oil which was identified by X H NMR and MS. EXAMPLE 375 To 3-methyl-4-methoxyacetophenone (25.0 g, 152.24 mmol) in absolute ethanol (110 mL) in an erlenmeyer was added 3,5-dimethoxybenzaldehyde -354- (35.42 g, 208.88 mmol). The solution swirled while 10? sodixim hydroxide (11 mL) added. The mixture stirred 1 hour and allowed to stand to precipitate. The solid was collected by filtration and washed with ethanol (3 x 200 mL) . The solid was dried in vacuo giving 37.12 g (78%) of an off-white solid which was identified by X H NMR, MS, and microanalysis. EXAMPLE 376 To the chalcone, 375. (37.1 g, 119 mmol) in absolute ethanol (575 mL) at 55°C was added acetic acid (15.5 mL) followed by slow addition of potassium cyanide (19.34 g, 297 mmol) in water (80 mL) . The solution was stirred at reflux « 80°C for 24 hours. The solution was cooled and treated with water (225 mL) . The mixture was then decanted and the oily solid taken up in EtOAc (600 mL) . EtOAc washed with brine and dried (MgS0 4 ) and evaporated to give the nitrile 31.53 g (78%) as an oily solid. The nitrile was identified by X H NMR, MS, and microanalysis. - 355 - EXAMPLE 377 To the nitrile, 376. (31.53 g, 92.91 mmol) was added methanol (275 mL) . The mixture was saturated with HCl (g) and heated to reflux until no nitrile remained, by thin layer chromatography. The solution was cooled and treated with water (200 mL) . The resultant oily solid was decanted away and dissolved in 400 mL EtOAc, then washed with H 2 0 (2 x 150 mL) and brine (2 x 100 mL) . EtOAc layer dried (MgS0 4 ) and evaporated to the ester. This gave the ester 29.15 g (84%) as a dark oily solid which was identified by X H NMR, MS, and microanalysis. -356- EXAMPLE 378 Sodium 2-Benzo11.31dioxol-5-yl-3-cyclohexylmethyl- 4- (4-methoxy-phenyl) -4-oxo-but-2-enoate To methanol (50 mL) was added the pure butenolide, 221. (1.58 g, 3.74 mmol). Added to this 3.55 mL of a I.OION NaOH solution (3.59 mmol). Stirred solution 10 minutes, then filtered away small amount of insolubles through glass wool. Evaporated MeOH and residue taken up in distilled water (250 mL) . Washed aqueous solution with ethyl ether (100 mL) . The aqueous solution was concentrated to remove any ether present, then frozen in a -80°C bath. The frozen material was lyophilized to 1.33 g (80%) of a fluffy white solid. The butenolide salt was identified by X H NMR, MS, [M + H] + = 422 Da., and microanalysis; including water and Na analysis. -357- EXAMPLE 379 Sodium 3-Cyclohexylmethyl-2- (3.5-dimethoxy-phenyl) - 4- (4-methoxy-phenyl) -4-oxo-but-2-enoate To methanol (50 mL) was added the pure butenolide, 275. (1.67 g, 3.81 mmol), becoming a slurry. Added to this 3.62 mL of a I.OION NaOH solution (3.66 mmol), and all dissolved. Stirred solution 10 minutes, then filtered away small amount of insolubles through glass wool. Evaporated MeOH and residue taken up in distilled water (250 mL) . Washed aqueous solution with ethyl ether (125 mL) . The aqueous solution was concentrated to remove any ether present, then frozen in a -80°C bath. The frozen material was lyophilized to 1.25 g (71.4%) of a tan fluffy solid. The butenolide salt was identified by X H NMR, MS, [M + H] + = 438 Da. , and microanalysis; including water and Na analysis. -358- EXAMPLE 380 Sodium 2-Benzoll.31dioxol-5-yl-3- (4-methoxy-benzyl) - 4- (4-methoxy-phenyl) -4-oxo-but-2-enoate To methanol (215 mL) was added the pure butenolide, 72, (7.54 g, 16.89 mmol), becoming a slurry. Added to this 15.89 mL of a I.OION NaOH solution (16.045 mequiv of OH " ), and all dissolved. Stirred solution 10 minutes, then filtered away small amount of insolubles through glass wool. Evaporated MeOH and residue taken up in distilled water (350 mL) . Washed aqueous solution with ethyl ether (150 mL) . The aqueous solution was concentrated to remove any ether present, then frozen in a -80°C bath. The frozen material was lyophilized to 7.05 g (89%) of a white fluffy solid. The butenolide salt was identified by X H NMR, MS, [M + H] + = 446 Da., and microanalysis; including water and Na analysis. -359- EXAMPLE 381 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (3-methoxy- 4-octyloxy-benzyl) -5- (4-methoxy-phenyl) -5H-fu an-2-one To methanol (20 mL) was added sodium metal (88 mg, 3.81 mmol) and stirred to dissolve. To this was added the ester, 124. (1.30 g, 3.63 mmol) then 3-methoxy- 4-0-octylbenzaldehyde (1.06 g, 3.99 mmol). The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) • τlιe butenolide was isolated by evaporation of the appropriate fractions to give 323 mg (15.1%) as an orange oil. The butenolide was identified by X H NMR, MS, [M + H] + = 591 Da., and microanalysis. -360- EXAMPLΞ 382 3- (3.5-Dimethox -phenyl) -5-hydroxy-5- (4-methoxy- 3-methyl-phenyl) -4- (3.4.5-trimethoxy-benzyl) -5H-furan- 2-one To methanol (20 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 377. (1.49 g, 4.0 mmol) then 3,4,5-trimethoxybenzaldehyde (881 mg, 4.4 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 15% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 720 mg (33.5%) as a tan solid. The butenolide was identified by X H NMR, MS, [M + H] + = 537 Da., and microanalysis. -361- EXAMPLE 383 3-Benzo11.31dioxol-5-yl-5-hydroxy-5- (4-methoxy- 3-methyl-phenyl) -4- (3.4.5-trimethoxy-benzyl) -5H-furan- 2-one To methanol (14 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 289. (1.43 g, 4.0 mmol) then 3,4,5-trimethoxybenzaldehyde (881 mg, 4.4 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then slurried in 100 mL 10% EtOAc:CH 2 C1 2 and filtered to give 1.31 g (63%) as an off-white solid. The butenolide was identified by X H NMR, MS, [M + H] + = 521 Da., and microanalysis. -362- EXAMPLE 384 N-{4- [4-Benzo[1.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- 3-methyl-phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethy11 - phenyl}-acetamide To methanol (22 mL) was added sodium metal (148 mg, 6.42 mmol) and stirred to dissolve. To this was added the ester, 289. (2.18 g, 6.12 mmol) then 4-acetamidobenzaldehyde (1.15 g, 7.04 mmol). The mixture was heated to reflxix for 24 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and IN sodium hydroxide (40 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 100 mL EtOAc. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. Chromatographed crude; 10% EtOAc/CH 2 Cl 2 . Combined and evaporated appropriate ^ fractions. This gave the butenolide 2.05 g (70%) as a yellow solid. The butenolide was identified by X H NMR, MS, [M + H] + = 488 Da., and microanalysis. -363- EXAMPLE 385 N-{4- T4- (3.5-Dimethox -phenyl) -2-hydroxy-2- (4-methoxy- 3-methyl-phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 - phenyl}-acetamide To methanol (21 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 377. (1.49 g, 4.0 mmol) then 4-acetamido- benzaldehyde (719 mg, 4.4 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between EtOAc (200 mL) and IN sodium hydroxide (100 mL) . The aqueous phase was separated and acidified with 6N HCl. This acidic solution was extracted with 3 x 100 mL ethyl acetate. The organic phase was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. Chromatographed crude; 30% EtOAc/CH 2 Cl 2 . Combined and stripped appropriate fractions. This gave the butenolide 561 mg (27.9%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 504 Da., and microanalysis. -364- EXAMPLE 386 Potassium 3- (4-Acetylamino-benzyl) -2- (3.5-dimethoxy¬ phenyl) -4- (4-methoxy-3-methyl-phenyl) -4-oxo-but- 2-enoate To methanol (80 mL) was added the pure butenolide, 385. (3.26 g, 6.474 mmol), becoming a slurry. Added to this 5.76 mL of a 1.018N KOH solution (5.66 mmol), and all dissolved. Stirred solution 10 minutes, then filtered away small amount of insolubles through glass wool. Evaporated MeOH and residue taken up in distilled water (100 mL) . Washed aqueous solution with ethyl ether (100 mL) . The aqueous solution was concentrated to remove any ether present, then frozen in a -80°C bath. The frozen material was lyophilized to 2.93 g (93.9%) of a white fluffy powder. The butenolide salt was identified by X H NMR, MS, [M + H] + = 503 Da., and microanalysis; including water and K analysis. - 365 - EXAMPLE 387 Sodium 2-Benzon.3ldioxol-5-yl-4- (4-methoxy-3-methyl¬ phenyl) -4-OXO-3- (3.4.5-trimethoxy-benzyl) -but-2-enoate To methanol (110 mL) was added the pure butenolide, 383. (3.45 g, 6.63 mmol), becoming a slurry. Added to this 6.23 mL of a I.OION NaOH solution (6.30 mmol), and all dissolved. Stirred solution 10 minutes, then filtered away small amount of insolubles through glass wool. Evaporated MeOH and residue taken up in distilled water (120 mL) . Washed aqueous solution with ethyl ether (120 mL) . The aqueous solution was concentrated to remove any ether present, then frozen in a -80°C bath. The frozen material was lyophilized to 3.09 g (85.8%) of a white fluffy solid. The butenolide salt was identified by X H NMR, MS, [M + H] + = 520 Da., and microanalysis; including water and Na analysis. -366- EXAMPLE 388 3- (3.5-Dimethox -phenyl) -5-hydroxy-5- (4-methoxy- phenyl) -4- (3.4.5-trimethoxy-benzyl) -5H-furan-2-one To methanol (17 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 124. (1.43 g, 4.0 mmol) then 3,4,5-trimethoxybenzaldehyde (881 mg, 4.4 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 15% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 687 mg (32.7%) as a tan solid. The butenolide was identified by X H NMR, MS, [M + H] + = 523 Da., and microanalysis. -367- EXAMPLE 389 3- (3.5-Dimethox -phenyl) -5-hydroxy-4- (4-isopropoxy- 3-methoxy-benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (17 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 124. (1.43 g, 4.0 mmol) then 3-methoxy- 4-0-iPr-benzaldehyde (855 mg, 4.4 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 20% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 527 mg (25.1%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 521 Da., and microanalysis. -368- EXAMPLE 390 3- (3.5-Dimethox -phenyl) -5-hydroxy-4- (4-isopropoxy- 3-methoxy-benzyl) -5- (4-methoxy-3-methyl-phenyl) - 5H-furan-2-one To methanol (17 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 377. (1.49 g, 4.0 mmol) then 3-methoxy- 4-0-isopropylbenzaldehyde (855 mg, 4.4 mmol) . The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 72 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 540 mg (25.2%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 535 Da., and microanalysis. -369- EXAMPLE 391 3-Benzo11.31dioxol-5-yl-5-hydroxy-4- (4-isopropoxy- 3-methoxy-benzyl) -5- (4-methoxy-3-methyl-phenyl) - 5H-furan-2-one To methanol (23 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 289. (1.43 g, 4.0 mmol) then 3-methoxy- 4-0-isopropylbenzaldehyde (855 mg, 4.4 mmol) . The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 849 mg (41%) as an off-white foam. The butenolide was identified by X H NMR, MS, [M + H] + = 519 Da., and microanalysis. -370- EXAMPLE 392 2- (3.5-Dimethox -phenyl) -3- (4-methoxy-3-methyl-benzoyl- carbonyl) -4- (2.4.6-trimethoxy-phenyl) -but-2-enoic acid To methanol (20 mL) was added sodium metal (97 mg, 4.0 mmol) and stirred to dissolve. To this was the added ester, 377. (1.49 g, 4.0 mmol) then 2,4,6-trimethoxybenzaldehyde (881 mg, 4.4 mmol) . The mixture was heated to reflux for 72 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 50% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 240 mg tan solid. TLC showed slight impurity still present. Triturated solid in 50 mL Et 2 0 and filtered to give 103 mg (4.8%) as a tan solid. The butenolide was identified by X H NMR, MS, [M + H] + = 537 Da. , and microanalysis. -371- EXAMPLE 393 3- (3.5-Dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy- 3-methyl-phenyl) -4- (3-methoxy-4-octyloxy-benzyl) -5H- furan-2-one To methanol (20 mL) was added sodix_ιm metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 377. (1.49 g, 4.0 mmol) then 3-methoxy- 4-O-octylbenzaldehyde (1.16 g, 4.4 mmol) . The mixture was heated to reflxix for 48 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 458 mg (18.9%) as an orange oil. The butenolide was identified by X H NMR, MS, [M + H] + = 605 Da., and microanalysis. -372- EXAMPLE 394 3-Benzo11.31dioxol-5-yl-5-hydroxy-5- (4-methoxy- 3-methyl-phenyl) -4- (3-methoxy-4-octyloxy-benzyl) - 5H-furan-2-one To methanol (20 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 289. (1.43 g, 4.0 mmol) then 3-methoxy- 4-0-octylbenzaldehyde (1.16 g, 4.4 mmol) . The mixture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 48 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 830 mg (35%) as a tan gloss. The butenolide was identified by X H NMR, MS, [M + H] + = 589 Da., and microanalysis. -373- EXAMPLE 395 3-BenzoT1.31dioxol-5-yl-5-hydroxy-4- (4-isopropoxy- 3-methyl-benzyl) -5- (4-methoxy-3-methyl-phenyl) - 5H-furan-2-one To methanol (20 mL) was added sodixim metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 289. (1.43 g, 4.0 mmol) then 3-methyl- 4-0-isopropylbenzaldehyde (7.85 mg, 4.4 mmol). The mixture was heated to reflxix for 48 hours. The solution was then treated with acetic acid (4 mL) and refluxed an additional 72 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 5% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 786 mg (38%) as a pale yellow glass. The butenolide was identified by X H NMR, MS, [M + H] + = 503 Da., and microanalysis. -374- EXAMPLE 396 3- (3.5-Dimethox -phenyl) -5-hydroxy-4- (4-isopropoxy- 3-methyl-benzyl) -5- (4-methoxy-3-methyl-phenyl) - 5H-furan-2-one To methanol (20 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 377. (1.49 g, 4.0 mmol) then 3-methyl- 4-0-isopropylbenzaldehyde (785 mg, 4.4 mmol) . The itdxture was heated to reflux for 24 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 48 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 7% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 454 mg (22%) as a tan foam. The butenolide was identified by X H NMR, MS, [M + H] + = 519 Da., and microanalysis. -375- EXAMPLE 397 3-Benzo \1.31dioxol-5-yl-4- (4-cyclohexyloxy-3-methyl- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (20 mL) was added sodium metal (39.3 mg, 1.71 mmol) and stirred to dissolve. To this was added the ester, 19, (559 mg, 1.63 mmol) then 3-methyl-4-0-cyclohexylbenzaldehyde (392 mg, 1.80 mmol) . The mixture was heated to reflxix for 48 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 5% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 117.8 mg (13.6%) as a pale yellow oil. The butenolide was identified by X H NMR, MS, [M + H] + = 529 Da., and microanalysis. -376- EXAMPLE 398 3-Benzo[1.31dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) - 4- (1.2.3.4-tetrahydro-naphthalen-1-ylmethyl) -5H-furan- 2-one To methanol (12 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 1 , (1.37 g, 4.0 mmol) then α-tetralinyl- aldehyde (715 mg, 4.4 mmol) . The mixture was heated to reflux for 36 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 48 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 5% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 470 mg (25%) as a white foam. The butenolide was identified by X H NMR, MS, [M + H] + = 471 Da., and microanalysis. -377- EXAMPLE 399 3- r4-Benzo l.31dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 - cyclohexanecarboxylic acid methyl ester To methanol (20 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then ethyl-3-formyl- cyclohexanecarboxylate (810.7 mg, 4.4 mmol) . The mixture was heated to reflxix for 36 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 48 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 7% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 340 mg (17.2%) as a pale yellow foam. The butenolide was identified by X H NMR, MS, [M + H] + = 481 Da., and microanalysis. -378- EXAMPLE 400 3-Benzo11.31dioxol-5-yl-4-cyclopropylmethyl-5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (15 mL) was added sodium metal (97 mg, 4.2 mmol) and stirred to dissolve. To this was added the ester, 19., (1.37 g, 4.0 mmol) then cyclopropyl- carboxaldehyde (315 mg, 4.4 mmol) . The mixture was heated to reflxix for 48 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 48 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 7% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 163 mg (10.7%) as a white foam. The butenolide was identified by X H NMR, MS, [M + H] + = 381 Da., and microanalysis. -379- EXAMPLE 401 4-Benzyl-3- (2.5-dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (24 mL) was added sodixim metal (76.5 mg, 3.33 mmol) and stirred to dissolve. To this was added the ester, 374. (1.37 g, 3.17 mmol) then benzaldehyde (377.4 mg, 3.49 mmol). The mixture was heated to reflux for 72 hours. The solution was then treated with acetic acid (4.5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 630 mg (43.8%) as a white foam. The butenolide was identified by X H NMR, MS, [M + H] + = 433 Da., and microanalysis. -380- EXAMPLE 402 3- (2.5-Dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy- phenyl) -4- (3.4.5-trimethoxy-benzyl) -5H-furan-2-one To methanol (20 mL) was added sodium metal (84.2 mg, 3.66 mmol) and stirred to dissolve. To this was added the ester, 374. (1.25 g, 3.49 mmol) then 3,4,5-trimethoxybenzaldehyde (769 mg, 3.84 mmol) . The mixture was heated to reflux for 72 hours. The solution was then treated with acetic acid (5 mL) and refluxed an additional 48 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 15% EtOAc:CH 2 C1 2 ) . The butenolide was isolated by evaporation of the appropriate fractions to give 1.13 mg (62%) as a white foam. The butenolide was identified by X H NMR, MS, [M + H] + = 523 Da., and microanalysis. -381- EXAMPLE 403 3- l4-Benzoll.3]dioxol-5-yl-2-hydroxy-2- (4-methoxy- phenyl) -5-oxo-2.5-dihydro-furan-3-ylmethyl1 - cyclohexanecarboxylic acid To absolute ethanol (23 mL) was added sodixim metal (142.5 mg, 6.2 mmol) and stirred to dissolve. To this was added the ester, 19_, (2.05 g, 6.0 mmol) then ethyl- 3-formylcyclohexanecarboxylate (1179 mg, 6.4 mmol). The mixture was heated to reflux for 48 hours. The solution was then treated with acetic acid (5.5 mL) and refluxed an additional 24 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate (150 mL) and water (100 mL) . The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by MPL chromatography (silica gel, 10% EtOAc:CH 2 C1 2 ) . The ethyl ester butenolide was isolated by evaporation of the appropriate fractions to give 887 mg (30%) as a white foam. The ethyl ester butenolide was identified by X H NMR, MS, [M + H] + = 495 Da., and microanalysis. Then stirred 495 mg (1.0 mmol) of the ethyl ester butenolide in 8 mL MeOH and treated with 1.98 mL of a I.OION NaOH solution (2.0 mmol). Refluxed solution, 96 hours, then evaporated MeOH and partitioned residue - 382 - between 100 mL Et 2 0 and 150 mL H 2 0. Acidified aqueous layer (12% HCl) , then extracted with 150 mL EtOAc and washed with 100 mL H 2 0 and brine. Dried (MgS0 4 ) and stripped to 420 mg characterized [M + H] + = 467 Da., X H NMR, and microanalysis. EXAMPLE 404 3-Benzo11.3!dioxol-5-yl-5-hydroxy-4- (4-isopropyl- benzyl) -5- (4-methoxy-phenyl) -5H-furan-2-one To methanol (50 mL) was added sodium metal (190 mg, 8.2 mmol) and stirred to dissolve. To this was added the ester, 19., (2.67 g, 7.8 mmol) then 4-isopropylbenzaldehyde (1.53 mL, 10.1 mmol) . The mixture was heated to reflux for 4 hours. The solution was then treated with acetic acid (30 mL) and refluxed an additional 18 hours. The solvents were removed by evaporation, and the residue was partitioned between ethyl acetate and water. The organic phase was separated and dried over magnesium sulfate and evaporated to dryness. The crude product was then purified by flash chromatography (silica gel, 7:3 (hexane:ethyl acetate) . The butenolide was isolated by evaporation of the appropriate fractions to give 0.50 g -383 - (14%) as a foam. The butenolide was identified by X H NMR, IR, MS, [M + H] + = 459 Da., and microanalysis. EXAMPLE 405 1.3-Benzodioxol-5-acetic acid, o.- 11- 113- (methoxy- carbonyDphenyllmethyl1 -2- (4-methoxyphenyl) - 2-oxoethylenel - . monopotassium salt The butenolide, 286. (500 mg, 1.05 mmol) was stirred into 0.498N potassium hydroxide (in methanol), 2.11 mL (1.05 mmol) for 1 minute. The methanol evaporated in vacuo and the residue partitioned between water and ether. The aqueous phase frozen and lyophilized to give the salt 510 mg (95%) , which was identified by X H NMR, IR, MS, [M + H] + = 473 Da., and microanalysis. -384- EXAMPLE 406 1.3-Benzodioxole-5-acetic acid, α- 11- (4- methoxybenzoyl) -2- (2-methoxyphenyl)ethylidene1 - . monosodium salt. (Z) - To 284. (1.46 g, 3.27 mmol), in methanol (30 mL) was added I.OION sodium hydroxide (aq.) (3.05 mL, 3.07 mmol). The solution stirred for 5 minutes and evaporated free of methanol. The residue was partitioned between ether (150 mL) and distilled water (100 mL) . The aqueous phase separated, evaporated free of residual organic solvents, frozen and lyophilized. This gave 1.21 g (85%) of the butenolide salt as a white solid, which was identified by X H NMR, MS, [M + H] (±) - 447, IR, and microanalysis.

Claims: -385 - CLAIMS A compound of formula or a tautomeric open chain keto-acid form thereof or a pharmaceutically acceptable salt thereof wherein R x is alkyl sxibstituted or unsubstituted, straight, or branched, of from 1 to 12 carbon atoms, cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, phenyl substituted with from 1 to 5 substituents, naphthyl unsubstituted or substituted with from 1 to 5 substituents, or heteroaryl unsubstituted or substituted with from 1 to 5 substituents; R 2 is alkyl sxibstituted or unsubstituted straight, or branched of from 1 to 12 carbon atoms, cycloalkyl sxibstituted or unsubstituted of from 3 to 12 carbon atoms, aryl which is xinsxibstituted or sxibstituted with from 1 to 5 sxibstituents, heteroaryl which is xinsxibstituted or substituted with from 1 to 3 substituents; R 3 is alkyl sxibstituted or xmsubstituted straight, or branched, of from 1 to 12 carbon atoms, -386 - cycloalkyl substituted or unsubstituted of from 3 to 12 carbon atoms, aryl which is unsubstituted or substituted with from 1 to 5 substituents, heteroaryl which is unsubstituted or substituted with from 1 to 3 substituents; R 4 is hydrogen, hydroxy, halogen, SR 5 , 0R 5 wherein R 5 is alkyl or substituted alkyl of from 1 to 7 carbon atoms, NR 6 R 7 wherein R 6 and R 7 are each independently hydrogen, alkyl, substituted alkyl, sxibstituted or unsubstituted phenyl, and (CH 2 ) n OR 5 wherein n is an integer of from 1 to 3; X is oxygen, S or NR 8 wherein R 8 is hydrogen, alkyl or substituted alkyl with the proviso that when R x is monosubstituted phenyl and the substituent is p-methoxy, R 3 is not unsubstituted phenyl, monosubstituted phenyl, or mesityl and with the further proviso when R 2 is alkyl sxibstituted, the substituent is not oxygen at the α-position to the furanone ring and with the further proviso that R x and R 3 are not both alkyl or alkyl sxibstituted in the same molecule. 2. A compound according to Claim 1 wherein R x is phenyl substituted with from 1 to 5 substituents, naphthyl unsubstituted or substituted with from 1 to 5 substituents, or -387- heteroaryl unsubstituted or substituted with from 1 to 5 substituents; R 2 is alkyl substituted or unsubstituted straight, or branched, of from 1 to 7 carbon atoms, R 3 is aryl substituted or unsubstituted, heteroaryl substituted or unsubstituted; R 4 is hydroxy, OR 5 , or SR 5 ; X is 0 or S; with the proviso that when R x is monosubstituted phenyl and the substituent is p-methoxy, R 3 is not unsubstituted phenyl, monosubstituted phenyl, or mesityl and with the further proviso that when R 2 is alkyl substituted the substituent is not oxygen at the α-position to the furanone. 3. A compound according to Claim 1 wherein R x is 4-piperonyl, 3,4-dichlorophenyl, 3-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methoxy-4,5-methylenedioxyphenyl; R 2 is benzyl, 4-piperonylmethyl, 4-isopropylbenzyl, 1-naphthylmethyl, 2-naphthylmethyl, 3-thiophenylmethyl, 2-thiophenylmethyl, 3,4-dichlorobenzy1, • 388- 3 (N-Me)indolylmethyl, 3,4-dimethoxybenzyl, 4-Me 2 aminobenzyl, 4-isopropylbenzyl, 4-chlorobenzy1, 4-methoxybenzyl, 4-methylbenzyl, 3-methylbenzyl, 4-isopropoxybenzyl, 4-acetamidobenzyl, 4- ethylsulfonylbenzyl, 3-methyl-4-methoxybenzyl, 3-allyloxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3-n-propoxybenzyl, 4- hiomethylbenzyl, 3-carbethoxybenzyl, 4-carbethoxybenzyl, 3-methoxybenzyl, 2-methoxybenzyl, or 3-chlorobenzyl; R 3 is phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 3-methoxyphenyl , 3-methyl-4-methoxyphenyl, 3,4-dimethoxyphenyl, or 2,4-dimethoxyphenyl; R 4 is hydroxy, 0CH 3 , 0CH 2 CH0, OCH 2 COOH, - 389 - OCH 2 CH(OH)CH 2 OH, or OCH 2 (m-OH-phen l) , and X is oxygen. 4. A compound according to Claim 1 wherein R is 4-piperonyl, 3,5-dimethoxyphenyl, or 3-methoxy-4,5-methylenedioxyphenyl; R 2 is 4-piperonylmethyl, 4-isopropylbenzyl, 2-naphthylmethyl, 1-naphthylmethyl, benzyl, 2-thiophenylmethy1, 3-thiophenylmethyl, 3- (N-Me)indolylmethyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 4-isopropoxybenzyl, 4-acetamidobenzyl, 4-methylsulfonylbenzyl, 3-methyl-4-methoxybenzyl, 3-allyloxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3-n-propoxybenzyl, 4-thiomethylbenzl, 3-carbethoxybenzyl, 4-carbethoxybenzyl, 2-methoxybenzyl, 3-methoxybenzyl, or 3-chlorobenzyl; R 3 is 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3-methyl-4-methoxyphenyl, or 2,4-dimethoxyphenyl; - 390 - R 4 is OH; and X is oxygen. 5. A compound selected from the group: 2 (5H) -furanone, 5- (4-chlorophenyl) -5-hydroxy- 3- [4- (1-methylethyl)phenyl] -4- (phenylmethyl) -, (±)-, (±) -3- (1,3-benzodioxol-5-yl) -5- (4-chloro- phenyl) -4- (phenylmethyl) -5- (2-propenyloxy) - 2(5H) -furanone, acetaldehyde, [ [4- (1,3-benzodioxol-5-yl) - 2- (4-chlorophenyl) -2,5-dihydro-5-oxo- 3- (phenylmethyl) -2-furanyl]oxo] -, (±) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- (2,3-dihydroxypropoxy) - 4- (phenylmethyl) -, (±) -, acetic acid, [[4- (1,3-benzodioxol-5-yl) - 2- (4-chlorophenyl) -2,5- ihydro-3- (phenylmethyl) - 5-oxo-2-furanyl]oxy] -, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- [(3-hydroxyphenyl)methoxy] - 4- (phenylmethyl) -, (±) -, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5- (phenylamino) -4- (phenyl¬ methyl)-, (±)- 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- (phenylmethyl) -5- [(phenyl- methyl)amino] -, (±) - 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methylphenyl) -4- (phenylmethyl) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5-phenyl-4- (phenylmethyl) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- henyl-4- (2-thienylmethyl) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5-phenyl-4- (3- hienylmethyl) -, - 391- 2 (5H) -furanone, 5- (4-chlorophenyl) - 3- (2,3-dihydro-l,4-benzodioxin-6-yl) -5-hydroxy- 4- (phenylmethyl) -, 2 (5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (2-thienylmethyl) -, 2 (5H) -furanone, 5- (4-chlorophenyl) -5-hydroxy- 3- [4- (1-methylethyl)phenyl] -4- (1-naphthalenyl¬ methyl) -, (±)-, 2(5H) -furanone, 5- (4-chlorophenyl) -5-hydroxy- 3- [4- (1-methylethyl)phenyl] -4- (2-naphthalenyl¬ methyl)-, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (1-naphthalenyl¬ methyl)-, (±)-, 2(5H) -furanone, 4- (1,3-benzodioxol- 5-ylmethyl) -5- (4-chlorophenyl) -5-hydroxy- 3- [4- (1-methylethyl) -phenyl] -, (±) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (2-naphthalenyl¬ methyl)-, (±)-, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- [[4- (1-methyl¬ ethyl)phenyl]methyl] -, (±) -, 2(5H) -furanone, 3- (1,3-benzodioxol-5-yl) - 4- (1,3-benzodioxol-5-ylmethyl) -5- (4-chlorophenyl) - 5-hydroxy-, (±)-, 2(5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -5-hydroxy-4- (3-thienylmethyl) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3 [4- (dimethylamino)phenyl] -5-hydroxy- 4- (phenylmethyl) -, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 4- [(3,4-dichlorophenyl)methyl] -3- [(4-dimethyl- amino)phenyl] -5-hydroxy, (±) -, -392 - 2(5H) -Furanone, 4- (1,3-benzodioxol- 5-ylmethyl) -5- (4-chlorophenyl) -3- [4- (dimethyl- amino)phenyl] -5-hydroxy-, (±) -, 2 (5H) -Furanone, 5- (4-chlorophenyl) - 3- [4- (dimethylamino)phenyl] -4- [ [4- (dimethylamino) phenyl]methyl] -5-hydroxy-, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 4- [ (3,4-dimethoxyphenyl)methyl] -3- [4- (dimethyl- amino)phenyl] -5-hydroxyphenyl)methyl] - 3- [4- (dimethylamino)phenyl] -5-hydroxy-, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dichlorophenyl) -5-hydroxy-4- (phenyl- methyl)-, (±)-, 2(5H) -Furanone, 4- (1,3-benzodioxol- 5-ylmethyl) -5- (4-chlorophenyl) -3- (3,4-dimethoxy¬ phenyl) -5-hydroxy, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -5-hydroxy- 4- (phenylmethyl) -, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -4- [(3,4-dimethoxy¬ phenyl)methyl] -5-hydroxy-, (±) -, 2(5H) -Furanone, 4- (1,3-benzodioxol- 5-ylmethyl) -5- (4-chlorophenyl) -3- (3,4-dichloro¬ phenyl) -5-hydroxy-, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -5-hydroxy- 4- [[4- (1-methylethyl)phenyl]methyl)-, (±)-, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -5-hydroxy- 4- [[4- (1-methylethyl)phenyl]methyl] -, (±) -, 2(5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -4- [[4- (dimethyl¬ amino)phenyl]methyl] -5-hydroxy-, (±) -, - 393 - 2 (5H) -Furanone, 5- (4-chlorophenyl) - 3- (3,4-dimethoxyphenyl) -4- [ [4- (dimethylamino) - phenyl]methyl] -5-hydroxy- , (±) - , 2 (5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- (phenylmethyl) -5-propoxy- , (±)-, 2 (5H) -Furanone, 5- (4-chlorophenyl) - 4- [ (3,4-dichlorophenyl)methyl] -3- (3,4-dimethoxy- phenyl) -5-hydroxy- , (±) - , 2 (5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5- (4-chlorophenyl) -4- [ (3-chlorophenyl)methyl] - 5-hydroxy, 3-Benzo[l,3]dioxol-5-yl-4- (4-chlorobenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (4-bromobenzyl) - 5-hydroxy-5- (4-methoxy-henyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (4-benzyloxy- benzyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4- (4-triflubromethylbenzyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one, 3- (4-Chlorophenyl) -5-hydroxy-4- (4-methoxy¬ benzyl) -5- (4-methoxyphenyl) -5H-furan-2-one, 5-Hydroxy-4- (4-methoxybenzyl) -3,5-bis- (4-methoxyphenyl) -5H-furan-2-one, 5-Hydroxy-4- (4-methoxybenzyl) -5- (4-methoxy- phenyl) -3-p-tolyl-5H-furan-2-one, 5-Hydroxy-4- (4-methoxybenzyl) -5- (4-methoxy¬ phenyl) -3-phenyl-5H-furan-2-one, 4-Benzyl-3- (2,4-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one, - 394 - 3- (3,4-Dichlorophenyl) -5-hydroxy- 4- (4-methoxybenzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 5- (4-Chlorophenyl) -3- (3,4-dichlorophenyl) - 140 5-hydroxy-4- (4-isopropylbenzyl) -5H-furan-2-one, 5- (4-Chlorophenyl) -3- (3,4-dichlorophenyl) - 4- (4-dimethylaminobenzyl) -5-hydroxy-5H-furan- 2-one, 4-Benzyl-3- (3,4-dichlorophenyl) -5-hydroxy- 145 5- (4-methoxyphenyl) -5H-furan-2-one, 4- (3,5-Dichlorobenzyl) -3- (3,5-dimethoxy- phenyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan- 2-one, 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 150 3- (2,3,4,5,6-pentafluorophenyl) -5H-furan-2-one, 4-Benzyl-3- (3,4-difluorophenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,4-Difluorophenyl) -5-hydroxy- 4- (4-isopropylbenzyl) -5- (4-methoxyphenyl) - 155 5H-furan-2-one, 3- (3,4-Difluorophenyl) -4- (4-dimethylamino- benzyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan- 2-one, 4-Benzyl-3- (3,5-dichlorophenyl) -5-hydroxy- 160 5- (4-methoxyphenyl) -5H-furan-2-one, 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 3- (3-methoxyphenyl) -5H-furan-2-one, 5-Hydroxy-5- (4-methoxyphenyl) -3- (3-methoxy¬ phenyl) -4- (3-propoxybenzyl) -5H-furan-2-one, 165 3-Benzo[l,3]dioxol-5-yl-4-benzyl- 5- (2,6-difluorophenyl) -5-hydroxy-5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4-pyridin-3-ylmethyl-5H-furan- 2-one, - 395 - 170 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 4-isoquinolin-4-ylmethyl-5- (4-methoxyphenyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-biphenyl- 4-ylmethyl-5-hydroxy-5- (4-methoxyphenyl) -5H-furan- 175 2-one, 2 (5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-4- (4-isoquinolinyl) -5- (4-methoxy- phenyl)-, (±)-, monohydrochloride, 2(5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 180 5-hydroxy-5- (4-methoxyphenyl) -4- (3-pyridinyl- methyl) -, (±) -, monohydrochloride, 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 3- (1-methyl) -lH-indol-3-yl) -5H-furan-2-one, 2-Butenoic acid, 2- (1,3-benzodioxol-5-yl) - 185 3- [(4-methoxy-4-methylphenyl)methyl] -4- (4-methoxy- phenyl) -4-oxo-, (Z)-, ion(l-) compd. with 2-hydroxy-N,N,N-trimethylethanaminium (1:1) , 2-Butenoic acid, 2- (1,3-benzodioxol-5-yl) - 4- (4-methoxyphenyl)-4-oxo-3- [[4-trifluoromethyl) - 190 phenyl]methyl] -, (Z)-, ion(l-) compd. with 2-hydroxy-N,N,N-trimethylethanaminium (1:1) , 4' -Benzyl-5' -hydroxy-5' - (4-methoxyphenyl) - 5'H- [2,3']bifuranyl-2-one, 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 195 3-thioophen-2-yl-5H-furan-2-one, 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 5H- [3,3']bifuranyl-2-one, 3-Benzo[l,3]dioxol-5-yl-4-benzyl- 5- (3,4-dimethoxyphenyl) -5-hydroxy-5H-furan-2-one, 200 3-Benzo[l,3]dioxol-5-yl-4-benzyl-5- (3,4-dichlorophenyl) -5-hydroxy-5H-furan-2-one, 4- (4-Benzo[l,3]dioxol-5-yl-3-benzyl- 2-hydroxy-5-oxo-2,5-dihydrofuran-2-yl)benzoic acid methyl ester, -396- 205 4- [4-Benzo[l,3]dioxol-5-yl-3-benzyl- 2-hydroxy-5-oxo-2,5-dihydrofuran-2-yl)benzoic acid, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5- (4-isopropylphenyl) -5H-furan-2-one, 210 3-Benzo[l,3]dioxol-5-yl-4-benzyl-5- (4-benzyl- oxyphenyl) -5-hydroxy-5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-benzyl- 5- (3,4-dimethylphenyl) -5-hydroxy-5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4-benzyl-5-hydroxy- 215 5-o-tolyl-5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5- (3-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5-methoxy- 5- (4-methoxyphenyl) -5H-furan-2-one, 220 3-Benzo[l,3]dioxol-5-yl-4-benzyl- 5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5-m-tolyl-5H-furan-2-one, 4-Benzyl-5-hydroxy-5- (4-methoxyphenyl) - 225 3-(3,4,5-trimethoxyphenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4-benzyl-5- (3-chloro- phenyl) -5-hydroxy-5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4- (4-methylsulfanylbenzyl) - 230 5H-furan-2-one, 3,5-Bis-benzo[l,3]dioxol-5-yl-4-benzyl- 5-hydroxy-5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5- (2-methoxyphenyl) -5H-furan-2-one, 235 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4-naphthalen-l-ylmethyl- 5H-furan-2-one, [R-(R*,S*)] and [S- (R*,R*)]carbamic acid, (1-phenylethyl) -, 4- (l,3-benzodioxol-5-yl) - - 397 - 240 2,5-dihydro-2- (4-methyoxyphenyl) -5-oxo- 3- (phenylmethyl) -2-furanyl ester, 3-Benzo[l,3]dioxol-5-yl-4-benzyl-5- (4-chloro- phenyl) -5- ydroxy-1,5-dihydropyrrol-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- 245 (4-methoxyphenyl) -4- (2-phenoxybenzyl-5H-furan- 2-one, 4-Benzyl-3- (3,4-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one, 2H-Pyrrole-2-one, 3- (1,3-benzodioxol-5-yl) - 250 l,5-dihydro-5-hydroxy-4,5-bis(4-methoxyphenyl) -, ±-, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5- (4-ethylphenyl) -5-hydroxy-5H-furan-2-one, 3- [4- (3,5-Dimethoxyphenyl) -2-hydroxy- 255 2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran- 3-ylmethyl]benzoic acid, 3-Benzo[1,3]dioxol-5-yl-4-benzyl-5-hydroxy- 5- (4-methylsulfanylphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- 260 (4-methoxy-3-methylbenzyl) -5- (4-methoxyphenyl) - 5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) -4- (4-methylbenzyl) -5H-furan- 2-one, 265 4- (4-Chlorobenzyl) -3- (3,5-dimethoxyphenyl) - 5-hydroxy-5- (4-methoxyphenyl).-5H-furan-2-one, 2(5H) -Furanone, 4- (cyclohexylmethyl) -3- (3,5-dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- phenyl) -, 270 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- (2-methoxybenzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-5- (4-methoxyphenyl) -4- (2-methylbenzyl) -5H-furan- 275 2-one, - 398 - 4- (2-Chlorobenzyl) -3- (3,5-dimethoxyphenyl) - 5-hydroxy-5- (4-methoxyphenyl-5H-furan-2-one, 4- [4-benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran- 280 3-ylmethyl]benzoic acid, 1,3-Benzodioxol-5-acetic acid, α- [2- [ (4-carboxyphenyl)methyl] -2- (4-methoxybenzoyl) - ethylidene] -, disodium salt, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- 285 (4-methoxyphenyl) -4- (3,4,5-trimethoxy-benzyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (2-chlorobenzyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- 290 (4-methoxyphenyl) -4- (2-methylbenzyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (2-methoxybenzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 295 3-Benzo[l,3]dioxol-5-yl-5-hydroxy-4,5-bis- (4-methoxyphenyl) -5H-furan-2-one, 3- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -benzoic acid, 300 {4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -phenyl}-acetic acid, {3- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 305 3-ylmethyl] -phenyl}-acetic acid, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-isopro-poxy-3,5-dimethyl-benzyl) - 5- (4-methoxy-phenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (3,5-dimethyl- 310 4-octyloxy-benzyl) -5-hydroxy-5- (4-methoxy-phenyl) 5H-furan-2-one, - 399 - 3-Benzo[1,3] ioxol-5-yl-4- (6,6-dimethyl- bicyclo[3.1.1] ept-2-en-2-ylmethyl) -5-hydroxy- 5- (4-methoxy-phenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) -4- (2-phenoxy-benzyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (2-cyclohexyl- ethyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-methoxy-5- (4-methoxy-phenyl) -4- (3,4,5-trimethoxy-benzyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (2-cyclohexyl- 2-phenyl-ethyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (2-cyclohexyl- 2-phenyl-ethyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, 3- (2-Allyloxy-5-methoxy-phenyl) -4-benzyl- 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-cycloheptylmethyl- 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) -4-pentyl-5H-furan-2-one, [2- (4-Benzo[l,3]dioxol-5-yl-3-benzyl- 2-hydroxy-5-oxo-2,5-dihydro-furan-2-yl) -5-methoxy- phenoxy] -acetic acid, {2- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -5-methoxy-phenoxy}-acetic acid, 2-Butenoic acid, 2- (1,3-benzodioxol-5-yl) - 4- [4- (lH-imidazol-l-yl)phenyl]4-oxo-3- (phenyl¬ methyl) -, 2-Benzo[l,3]dioxol-5-yl-4- (4-methoxy-phenyl) ■ 3- [4- (2-morpholin-4-yl-ethylcarbamoyl) -benzyl] - 4-oxo-but-2-enoic acid, -400- Benzamide, 4- [[4- (1,3-benzodioxol-5-yl) - 2,5-dihydro-2-hydroxy-2- (4-methoxyphenyl) -5-oxo- 350 3-furanyl]methyl] -N- [2- (4-morpholinyl)ethyl] -, monohydrochloride, (+/-)-, {4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -2,6-dimethoxy-phenoxy}-acetic acid, 355 2- (3,5-Dimethoxy-phenyl) -3- (4-methoxy- 3-methyl-benzoyl-carbonyl) -4- (2,4,6-trimethoxy- phenyl) -but-2-enoic acid, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-5- (4-methoxy-3-methyl-phenyl) -4- (3-methoxy- 360 4-octyloxy-benzyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy-3-methyl-phenyl) -4- (3-methoxy- 4-octyloxy-benzyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (4-cyclohexyloxy- 365 3-methyl-benzyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) -4- (1,2,3,4-tetrahydro- naphthalen-1-ylmethyl) -5H-furan-2-one, 370 3- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -cyclohexanecarboxylic acid, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4-isopropyl-benzyl) -5- (4-methoxy-phenyl) - 375 5H-furan-2-one. 6. A compound named: 2 (5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methoxyphenyl) -4- (phenylmethyl) -, 3-Benzo[1,3]dioxol-5-yl-4-(3-chlorobenzyl) ■ 5 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, - 401 - 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) -4- (4-methylbenzyl) -5H-furan- 2-one, 3-Benzo[l,3]dioxol-5-yl-5-hydroxy-4- (4-methoxybenzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-4- (4-tert- butylbenzyl) -5-hydroxy-5- (4-methoxyphenyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4- (4-methylbenzyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4- (3-trifluoromethylbenzyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 4- (isopropoxybenzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-4- (4-dimethylamino- benzyl) -5-hydroxy-5- (4-methoxyphenyl) -5H-furan- 2-one, 3-Benzo[l,3]dioxol-5-yl-4-benzo[1,3]dioxol- 5-ylmethyl-5-hydroxy-5- (4-methoxyphenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 4- (4-methoxy-3-methylbenzyl) -5- (4-methoxyphenyl) - 5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4- (3-methylbenzyl) -5H-furan- 2-one, 3-Benzo[l,3]dioxol-5-yl-4- (3-chloro- 4-methoxybenzyl) -5-hydroxy-5- (4-methoxyphenyl) - 5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (4-butoxybenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, -402 - 3- (3,4-Dichlorohenyl) -5-hydroxy- 4- (4-isopropylbenzyl) -5- (4-methoxyphenyl) - 5H-furan-2-one, 4-Benzyl-3- (3,5-dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -4- (3-propoxybenzyl) -5H-furan- 2-one, 4- (3-Chloro-enzyl) -3- (3,5-dimethoxyphenyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -4- (3-trifluoromethylbenzyl) - 5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -4- (3-fluorobenzyl) - 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy- 4- (3-methoxybenzyl) -5- (4-methoxy-henyl) -5H-furan- 2-one, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy- 4- (4-methoxybenzyl) -5- (4-methoxyphenyl) -5H-furan- 2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy- 5- (4-methoxyphenyl) -4-pyridin-3-ylmethyl-5H-furan- 2-one, 3- [4- (3,5-Dimethoxyphenyl) -2-hydroxy- 2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran- 3-ylmethyl]benzaldehyde, 4- (3-Allyloxy-4-methoxy-enzyl) - 3- (3,5-dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- phenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 5- (4-methoxyphenyl) -4- (3-propoxybenzyl) -5H-furan- 2-one, 4- (3-Allyloxy-4-methoxy-enzyl) -3-benzo[l,3] - dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) - 5H-furan-2-one, -403 - 2 (5H) -Furanone, 3- (3,5-dimethoxyphenyl) - 5-hydroxy-5- (4-methoxyphenyl) -4- (3-pyridinyl- methyl) -, (±) -, monohydrochloride, 2-Butenoic acid, 2- (1,3-benzodioxol-5-yl) - 4- (4-methoxyphenyl) -4-oxo-3- (phenylmethyl) -, (Z)-, ion(l-) compound with 2-hydroxy- N,N,N-triethanaminium (1:1) , 4- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy- 2- (4-methoxyphenyl) -5-oxo-2,5-dihydrofuran- 3-ylmethyl]benzoic acid methyl ester, 3-Benzo[1,3]dioxol-5-yl-4-cyclohexylmethyl- 5-hydroxy-5- (4-methoxyphenyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 4- (4-methanesulfonylbenzyl) -5- (4-methoxyphenyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-benzyl- 5- (2,4-dimethoxyphenyl) -5-hydroxy-5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 4- (4-methoxy-2,5-dimethylbenzyl) -5- (4-methoxy- phenyl) -5H-furan-2-one, 2-Butenoic acid, 2- (1,3-benzodioxol-5-yl) - 4- (4-methoxyphenyl) -4-oxo-3- [ (3-propoxyphenyl) - methyl]-, (Z)-, ion(l-) compound with 2-hydroxy- N,N,N-trimethylethanaminium (1:1) , 3-Benzo[1,3]dioxol-5-yl-5-hydroxy- 4- (4-methoxy-2,3-dimethylbenzyl) -5- (4-methoxy- phenyl) -5H-furan-2-one, 4- (3-Allyloxy-4-methoxybenzyl) -3-benzo[l,3] - dioxol-5-yl-5-(2,4-dimethoxyphenyl) -5-hydroxy- 5H-furan-2-one, 3- (3,5-Dimethoxyphenyl) -5-hydroxy-4- (4-methoxy-3-methylbenzyl) -5- (4-methoxyphenyl) - 5H-furan-2-one, 2(5H) -Furanone, 4- (cyclohexylmethyl) -3- (3,5-dimethoxyphenyl) -5-hydroxy-5- (4-methoxy- phenyl) -, -404 - 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxyphenyl) -4- (3,4,5-trimethoxybenzyl) - 5H-furan-2-one, Benzoic acid, 3- [[4- (1,3-benzodioxol- 5-yl) -2,5-dihydro-2-hydroxy-2- (4-methoxyphenyl) - 5-oxo-3-furanyl]methyl] -, methyl ester, 2 (5H) -Furanone, 3- (1,3-benzodioxol-5-yl) - 5-hydroxy-5- (4-methoxy-3-methylphenyl) - 4- (phenylmethyl) -, (+/-)-, {4- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl)-5-oxo-2,5-dihydro-furan- 3-ylmethyl] -phenyl}-acetic acid methyl ester, {3- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -phenyl}-acetic acid methyl ester, 3-Benzo[l,3]dioxol-5-yl-5-hydroxy-4- (4-methoxy-3,5-dimethyl-benzyl) -5- (4-methoxy- phenyl) -5H-furan-2-one, 4-Benzyl-5-hydroxy-3- (7-methoxy-benzo[l,3] - dioxol-5-yl) -5- (4-methoxy-phenyl) -5g-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4- (3,5-dimethoxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan- 2-one, 3-Benzo[l,3]dioxol-5-yl-4- (3,4-dimethoxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) -4- (2 ,3,4-trimethoxy-benzyl) - 5g-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl)-4- (2,4,5-trimethoxy-benzyl) - 5g-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- (2,5-dimethoxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5g-furan- 2-one, -405 - 3-Benzo[1,3]dioxol-5-yl-4- (2,3-dimethoxy- benzyl) -5-hydroxy-5- (4-methoxy-phenyl) -5g-furan- 2-one, 3-Benzo[l,3]dioxol-5-yl-4- (4-benzyloxy- 3-methoxy-benzyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-4-cyclopentylmethyl- 5-hydroxy-5- (4-methoxy-phenyl) -5H-furan-2-one, 4ϋf-Naphtho[2,3-α]pyran-4-one, 2- (3-hydroxy- 4-methoxyphenyl) -, 3-Benzo[1,3]dioxol-5-yl-4-cyclohex-3-enyl- methyl-5-hydroxy-5- (4-methoxy-phenyl) -5H-furan- 2-one, 3-Benzo[1,3]dioxol-5-yl-4- (2-cyclopentyl- 2-phenyl-ethyl) -5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-4- [2- (benzo[1,3] - dioxol-5-yloxy) -benzyl] -5-hydroxy-5- (4-methoxy¬ phenyl) -5H-furan-2-one, 4- (2-Allyloxy-4-methoxy-benzyl) -3-benzo[l,3] dioxol-5-yl-5-hydroxy-5- (4-methoxy-phenyl) - 5H-furan-2-one, Sodium 2-benzo[1,3]dioxol-5-yl-3-benzyl-4- (4-methoxyphenyl) -4-oxobut-2-enoate, 1,3-Benzodioxol-5-acetic acid, α- [2- (4-methoxyphenyl) -1- [[4- (1-methylethoxy) - phenyl]methyl] -2-oxoethylene] -, (Z) -, choline salt, Sodium 2-benzo[1,3]dioxol-5-yl-3-benzyl-4- (4-methoxyphenyl) -4-oxobut-2-enoate, Sodium 2-benzo[1,3]dioxol-5-yl-3-benzyl-4- (4-methoxy-3-methylphenyl) -4-oxobut-2-enoate, 5-Hydroxy-3- (7-methoxy-benzo[1,3]dioxol- 5-yl) -5- (4-methoxy-phenyl) -4- (3,4,5-trimethoxy¬ benzyl) -5g-furan-2-one, - 406 - 4-Benzyl-5-hydroxy-3- (7-methoxy-benzo[1,3] - dioxol-5-yl) -5- (4-methoxy-3-methyl-phenyl) - 185 5H-furan-2-one, 5-Hydroxy-3- (7-methoxy-benzo[l,3]dioxol- 5-yl) -5- (4-methoxy-3-methyl-phenyl) -4- (3,4,5- trimethoxy-benzyl) -5g-furan-2-one, {4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- 190 (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -2,6-dimethoxy-phenoxy}-acetic acid ethyl ester, {5- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 195 3-ylmethyl] -2,3-dimethoxy-phenoxy}-acetic acid ethyl ester, {5- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy- 2- (4-methoxy-phenyl) -5-oxo-2,5-dihydro-furan- 3-ylmethyl] -2,3-dimethoxy-phenoxy}-acetic acid, 200 Sodixim 2-benzo[l,3]dioxol-5-yl-3-benzyl-4- (4-methoxy-3-methylphenyl) -4-oxobut-2-enoate, Sodium 2-benzo[l,3]dioxol-5-yl-3- (4-methoxy- benzoyl) -4- (4-methoxy-2,5-dimethylphenyl) -but- 2-enoate, 205 Sodium 3-benzyl-2- (7-methoxybenzo[1,3]dioxol■ 5-yl) -4- (4-methoxyphenyl) -4-oxobut-2-enoate, Sodium 2- (7-methoxybenzo- [1,3]dioxol-5-yl) - 3- (4-methoxy-3-methylbenzoyl-4- (3,4,5-trimethoxy- phenyl) -but-2-enoate, 210 Sodium 2- (7-methoxybenzo- [1,3]dioxol-5-yl) - 3- (4-methoxy-3-methylbenzoyl-4- (3,4,5-trimethoxy- phenyl) -but-2-enoate, Sodium 2- (7-methoxybenzo- [1,3]dioxol-5-yl) - 4- (4-methoxyphenyl) -4-oxo-3- (3,4,5-trimethoxy- 215 benzyl) -but-2-enoate, Sodium 2-Benzo[1,3]dioxol-5-yl-3-cyclohexyl- methyl-4- (4-methoxy-phenyl) -4-oxo-but-2-enoate, -407- Sodium 3-Cyclohexylmethyl-2- (3,5-dimethoxy¬ phenyl) -4- (4-methoxy-phenyl) -4-oxo-but-2-enoate, 220 Sodium 2-Benzo[1,3]dioxol-5-yl-3- (4-methoxy¬ benzyl) -4- (4-methoxy-phenyl) -4-oxo-but-2-enoate, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (3- methoxy-4-octyloxy-benzyl) -5- (4-methoxy-phenyl) - 5g-furan-2-one, 225 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-5- (4- methoxy-3-methyl-phenyl) -4- (3,4,5-trimethoxy¬ benzyl) -5H-furan-2-one, 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5- (4- methoxy-3-methyl-phenyl) -4- (3,4,5-trimethoxy- 230 benzyl) -5H-furan-2-one, N-{4- [4-Benzo[l,3]dioxol-5-yl-2-hydroxy-2- (4-methoxy-3-methyl-phenyl) -5-oxo-2,5-dihydro- furan-3-ylmethyl] -phenyl}-acetamide, N-{4- [4- (3,5-Dimethoxy-phenyl) -2-hydroxy-2- 235 (4-methoxy-3-methyl-phenyl) -5-oxo-2,5-dihydro- furan-3-ylmethyl] -phenyl}-acetamide, Potassium 3- (4-Acetylamino-benzyl) -2- (3,5- dimethoxy-phenyl) -4- (4-methoxy-3-methyl-phenyl) -4- oxo-but-2-enoate, 240 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-5- (4- methoxy-phenyl) -4- (3,4,5-trimethoxy-benzyl) -5g- furan-2-one, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (4- isopropoxy-3-methoxy-benzyl) -5- (4-methoxy-phenyl) - 245 5H-furan-2-one, 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (4- isopropoxy-3-methoxy-benzyl) -5- (4-methoxy-3- methyl-phenyl) -5H-furan-2-one, 3-Benzo[l,3]dioxol-5-yl-5-hydroxy-4- (4- 250 isopropoxy-3-methoxy-benzyl) -5- (4-methoxy-3- methyl-phenyl) -5g-furan-2-one, -408 - 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-4- (4- isopropoxy-3-methyl-benzyl) -5- (4-methoxy-3-methyl¬ phenyl) -5g-furan-2-one, 255 3- (3,5-Dimethoxy-phenyl) -5-hydroxy-4- (4- isopropoxy-3-methyl-benzyl) -5- (4-methoxy-3-methyl¬ phenyl) -5 -furan-2-one, 3- [4-Benzo[1,3]dioxol-5-yl-2-hydroxy-2- (4- methoxy-phenyl) -5-oxo-2,5-dihydro-furan-3- 260 ylmethyl] -cyclohexanecarboxylic acid methyl ester, 3-Benzo[1,3]dioxol-5-yl-4-cyclopropylmethyl- 5-hydroxy-5- (4-methoxy-phenyl) -5g-furan-2-one, l,3-Benzodioxol-5-acetic acid, α-[l-[[3- (methoxy-carbonyl)phenyl]methyl] -2- (4-methoxy- 265 phenyl) -2-oxoethylene] -, monopotassium salt, and l,3-Benzodioxole-5-acetic acid, α- [1- (4- methoxybenzoyl) -2- (2-methoxyphenyl)ethylidene] -, monosodium salt, (Z) - . 7. A compound selected from 2-benzo- [l,3]dioxol-5-yl- 4- (4-methoxyphenyl) -4-oxo-3- (3,4,5-trimethoxy¬ benzyl) -but-2-enoic acid and the pharmacologically acceptable salts thereof. 8. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to Claim 1 in admixture with a pharmaceutically acceptable excipient, diluent, and/or carrier. 9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula - 409 - or a pharmaceutically acceptable salt thereof wherein R χ is piperonyl, R 2 is phenyl, and R 3 -is p-chlorophenyl in admixture with a pharmaceu¬ tically acceptable excipient, diluent, and/or carrier. 10. A method of inhibiting elevated levels of endothelin comprising administering to a host suffering therefore a therapeutically effective amount of a composition according to Claim 1 in unit dosing form. 11. A method of inhibiting elevated levels of endothelin comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 7 in unit dosage form. 12. A method of treating hypertension comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 13. A method of treating diabetes comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 14. A method of treating congestive heart failure and myocardial infarction/myocardial ischemia - 410 - comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 15. A method of treating endotoxic shock comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 16. A method of treating subarachnoid hemorrhage comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 17. A method of treating subarachnoid hemorrhage comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 7 in unit dosage form. 18. A method of treating arrhythmias comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 19. A method of treating asthma comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 20. A method of treating acute and chronic renal failure comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. - 411 - 21. A method of treating preeclampsia comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 22. A method of treating cerebral ischemia and/or cerebral infarction comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 23. A method of treating cerebral ischemia and/or cerebral infarction comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 7 in unit dosage form. 24. A method of treating pulmonary hypertension comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 25. A method of treating ischemic disease comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 or Claim 8 in unit dosage form. 26. A method of protecting against gastric mucosal damage or treating ischemic bowel disease comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. - 412 - 27. A method of treating atherosclerotic disorders including Raynaud's disease comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 28. A method of treating restenosis comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 29. A method of treating angina comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 30. A method of treating cancer comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 31. A method of treating hemorrhagic shock comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. 32. A method of treating cirrhosis comprising administering to a host suffering therefrom a therapeutically effective amount of a compoxind according to Claim 1 in unit dosage form. 33. A method of treating septic shock comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form. - 413 - 34. A method of treating stroke comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Claim 1 in unit dosage form.

Inventors: BERRYMAN KENT ALAN, DOHERTY ANNETTE MARIAN, EDMUNDS JEREMY JOHN, PATT WILLIAM CHESTER, PLUMMER MARK STEPHEN, REPINE JOSEPH THOMAS, BERRYMAN, KENT, ALAN, DOHERTY, ANNETTE, MARIAN, EDMUNDS, JEREMY, JOHN, PATT, WILLIAM, CHESTER, PLUMMER, MARK, STEPHEN, REPINE, JOSEPH, THOMAS
Applicants: WARNER LAMBERT CO, WARNER-LAMBERT COMPANY
Application year: 1994
Main classification: C07D407
IPC codes: A61K31, A61P3, A61P9, A61P37, A61P43, C07C45, C07C47, C07C49, C07C59, C07D307, C07D317, C07D333, C07D405, C07D407, C07D409